Merges one or more HaplotypeCaller GVCF files into a single GVCF with appropriate annotations

Category Short Variant Discovery

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Overview

Combine per-sample gVCF files produced by HaplotypeCaller into a multi-sample gVCF file

CombineGVCFs is meant to be used for merging of GVCFs that will eventually be input into GenotypeGVCFs. One could use this tool to genotype multiple individual GVCFs instead of GenomicsDBImport; one would first use CombineGVCFs to combine them into a single GVCF and pass the results into GenotypeGVCFs. The main advantage of using CombineGVCFs over GenomicsDBImport is the ability to combine multiple intervals at once without building a GenomicsDB. CombineGVCFs is slower than GenomicsDBImport though, so it is recommended CombineGVCFs only be used when there are few samples to merge.

Input

Two or more HaplotypeCaller GVCFs to combine.

Output

A combined multi-sample gVCF.

Usage example

 gatk CombineGVCFs \
   -R reference.fasta \
   --variant sample1.g.vcf.gz \
   --variant sample2.g.vcf.gz \
   -O cohort.g.vcf.gz
 

Caveats

Only GVCF files produced by HaplotypeCaller (or CombineGVCFs) can be used as input for this tool. Some other programs produce files that they call GVCFs but those lack some important information (accurate genotype likelihoods for every position) that GenotypeGVCFs requires for its operation.

If the GVCF files contain allele specific annotations, add `-G Standard -G AS_Standard` to the command line.

Users generating large callsets (1000+ samples) may prefer GenomicsDBImport, which uses Intel's GenomicsDB and is capable of scaling to much larger sample sizes than CombineGVCFs. This tool provides a pure java reference implementation of the combine operation which is available on all architectures.

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Additional Information

Read filters

This Read Filter is automatically applied to the data by the Engine before processing by CombineGVCFs.

• WellformedReadFilter

CombineGVCFs specific arguments

This table summarizes the command-line arguments that are specific to this tool. For more details on each argument, see the list further down below the table or click on an argument name to jump directly to that entry in the list.

Argument name(s)	Default value	Summary
Required Arguments
--output  -O	null	The combined GVCF output file
--reference  -R	null	Reference sequence file
--variant  -V	[]	One or more VCF files containing variants
Optional Tool Arguments
--annotation  -A	[]	One or more specific annotations to add to variant calls
--annotation-group  -G	[]	One or more groups of annotations to apply to variant calls
--annotations-to-exclude  -AX	[]	One or more specific annotations to exclude from variant calls
--arguments_file	[]	read one or more arguments files and add them to the command line
--break-bands-at-multiples-of	0	If > 0, reference bands will be broken up at genomic positions that are multiples of this number
--cloud-index-prefetch-buffer  -CIPB	-1	Size of the cloud-only prefetch buffer (in MB; 0 to disable). Defaults to cloudPrefetchBuffer if unset.
--cloud-prefetch-buffer  -CPB	40	Size of the cloud-only prefetch buffer (in MB; 0 to disable).
--convert-to-base-pair-resolution	false	If specified, convert banded gVCFs to all-sites gVCFs
--dbsnp  -D	null	dbSNP file
--disable-bam-index-caching  -DBIC	false	If true, don't cache bam indexes, this will reduce memory requirements but may harm performance if many intervals are specified. Caching is automatically disabled if there are no intervals specified.
--disable-sequence-dictionary-validation	false	If specified, do not check the sequence dictionaries from our inputs for compatibility. Use at your own risk!
--drop-somatic-filtering-annotations	false	For input somatic GVCFs (i.e. from Mutect2) drop filtering annotations
--founder-id	[]	Samples representing the population "founders"
--gcs-max-retries  -gcs-retries	20	If the GCS bucket channel errors out, how many times it will attempt to re-initiate the connection
--gcs-project-for-requester-pays	""	Project to bill when accessing "requester pays" buckets. If unset, these buckets cannot be accessed.
--help  -h	false	display the help message
--input-is-somatic	false	Merge input GVCFs according to somatic (i.e. Mutect2) annotations (BETA)
--interval-merging-rule  -imr	ALL	Interval merging rule for abutting intervals
--intervals  -L	[]	One or more genomic intervals over which to operate
--pedigree  -ped	null	Pedigree file for determining the population "founders"
--sites-only-vcf-output	false	If true, don't emit genotype fields when writing vcf file output.
--version	false	display the version number for this tool
Optional Common Arguments
--add-output-sam-program-record	true	If true, adds a PG tag to created SAM/BAM/CRAM files.
--add-output-vcf-command-line	true	If true, adds a command line header line to created VCF files.
--create-output-bam-index  -OBI	true	If true, create a BAM/CRAM index when writing a coordinate-sorted BAM/CRAM file.
--create-output-bam-md5  -OBM	false	If true, create a MD5 digest for any BAM/SAM/CRAM file created
--create-output-variant-index  -OVI	true	If true, create a VCF index when writing a coordinate-sorted VCF file.
--create-output-variant-md5  -OVM	false	If true, create a a MD5 digest any VCF file created.
--disable-read-filter  -DF	[]	Read filters to be disabled before analysis
--disable-tool-default-read-filters	false	Disable all tool default read filters (WARNING: many tools will not function correctly without their default read filters on)
--exclude-intervals  -XL	[]	One or more genomic intervals to exclude from processing
--gatk-config-file	null	A configuration file to use with the GATK.
--input  -I	[]	BAM/SAM/CRAM file containing reads
--interval-exclusion-padding  -ixp	0	Amount of padding (in bp) to add to each interval you are excluding.
--interval-padding  -ip	0	Amount of padding (in bp) to add to each interval you are including.
--interval-set-rule  -isr	UNION	Set merging approach to use for combining interval inputs
--lenient  -LE	false	Lenient processing of VCF files
--QUIET	false	Whether to suppress job-summary info on System.err.
--read-filter  -RF	[]	Read filters to be applied before analysis
--read-index	[]	Indices to use for the read inputs. If specified, an index must be provided for every read input and in the same order as the read inputs. If this argument is not specified, the path to the index for each input will be inferred automatically.
--read-validation-stringency  -VS	SILENT	Validation stringency for all SAM/BAM/CRAM/SRA files read by this program. The default stringency value SILENT can improve performance when processing a BAM file in which variable-length data (read, qualities, tags) do not otherwise need to be decoded.
--seconds-between-progress-updates	10.0	Output traversal statistics every time this many seconds elapse
--sequence-dictionary	null	Use the given sequence dictionary as the master/canonical sequence dictionary. Must be a .dict file.
--tmp-dir	null	Temp directory to use.
--use-jdk-deflater  -jdk-deflater	false	Whether to use the JdkDeflater (as opposed to IntelDeflater)
--use-jdk-inflater  -jdk-inflater	false	Whether to use the JdkInflater (as opposed to IntelInflater)
--verbosity	INFO	Control verbosity of logging.
Advanced Arguments
--combine-variants-distance	0	Maximum distance for variants to be grouped together
--disable-tool-default-annotations	false	Disable all tool default annotations
--enable-all-annotations	false	Use all possible annotations (not for the faint of heart)
--ignore-variants-starting-outside-interval	false	Restrict variant output to sites that start within provided intervals (only applies when an interval is specified)
--max-distance	2147483647	Maximum distance for variants to be grouped together
--ref-padding	1	Number of bases on either side to expand spanning reference window
--showHidden	false	display hidden arguments

Argument details

Arguments in this list are specific to this tool. Keep in mind that other arguments are available that are shared with other tools (e.g. command-line GATK arguments); see Inherited arguments above.

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--add-output-sam-program-record / -add-output-sam-program-record

If true, adds a PG tag to created SAM/BAM/CRAM files.

boolean  true

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--add-output-vcf-command-line / -add-output-vcf-command-line

If true, adds a command line header line to created VCF files.

boolean  true

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--annotation / -A

One or more specific annotations to add to variant calls
Which annotations to include in variant calls in the output. These supplement annotations provided by annotation groups.

List[String]  []

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--annotation-group / -G

One or more groups of annotations to apply to variant calls
Which groups of annotations to add to the output variant calls. Any requirements that are not met (e.g. failing to provide a pedigree file for a pedigree-based annotation) may cause the run to fail.

List[String]  []

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--annotations-to-exclude / -AX

One or more specific annotations to exclude from variant calls
Which annotations to exclude from output in the variant calls. Note that this argument has higher priority than the -A or -G arguments, so these annotations will be excluded even if they are explicitly included with the other options.

List[String]  []

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--arguments_file / NA

read one or more arguments files and add them to the command line

List[File]  []

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--break-bands-at-multiples-of / NA

If > 0, reference bands will be broken up at genomic positions that are multiples of this number
To reduce file sizes our gVCFs group similar reference positions into bands. However, there are cases when users will want to know that no bands span across a given genomic position (e.g. when scatter-gathering jobs across a compute farm). The option below enables users to break bands at pre-defined positions. For example, a value of 10,000 would mean that we would ensure that no bands span across chr1:10000, chr1:20000, etc. Note that the --convert-to-base-pair-resolution argument is just a special case of this argument with a value of 1.

int  0  [ [ -∞  ∞ ] ]

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--cloud-index-prefetch-buffer / -CIPB

Size of the cloud-only prefetch buffer (in MB; 0 to disable). Defaults to cloudPrefetchBuffer if unset.

int  -1  [ [ -∞  ∞ ] ]

---

--cloud-prefetch-buffer / -CPB

Size of the cloud-only prefetch buffer (in MB; 0 to disable).

int  40  [ [ -∞  ∞ ] ]

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--combine-variants-distance / NA

Maximum distance for variants to be grouped together

int  0  [ [ -∞  ∞ ] ]

---

--convert-to-base-pair-resolution / NA

If specified, convert banded gVCFs to all-sites gVCFs

boolean  false

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--create-output-bam-index / -OBI

If true, create a BAM/CRAM index when writing a coordinate-sorted BAM/CRAM file.

boolean  true

---

--create-output-bam-md5 / -OBM

If true, create a MD5 digest for any BAM/SAM/CRAM file created

boolean  false

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--create-output-variant-index / -OVI

If true, create a VCF index when writing a coordinate-sorted VCF file.

boolean  true

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--create-output-variant-md5 / -OVM

If true, create a a MD5 digest any VCF file created.

boolean  false

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--dbsnp / -D

dbSNP file
A dbSNP VCF file.

FeatureInput[VariantContext]  null

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--disable-bam-index-caching / -DBIC

If true, don't cache bam indexes, this will reduce memory requirements but may harm performance if many intervals are specified. Caching is automatically disabled if there are no intervals specified.

boolean  false

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--disable-read-filter / -DF

Read filters to be disabled before analysis

List[String]  []

---

--disable-sequence-dictionary-validation / -disable-sequence-dictionary-validation

If specified, do not check the sequence dictionaries from our inputs for compatibility. Use at your own risk!

boolean  false

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--disable-tool-default-annotations / -disable-tool-default-annotations

Disable all tool default annotations
Hook allowing for the user to remove default annotations from the tool

boolean  false

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--disable-tool-default-read-filters / -disable-tool-default-read-filters

Disable all tool default read filters (WARNING: many tools will not function correctly without their default read filters on)

boolean  false

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--drop-somatic-filtering-annotations / NA

For input somatic GVCFs (i.e. from Mutect2) drop filtering annotations
Rather than move the per-sample INFO annotations used for filtering to the FORMAT field, drop them entirely. This makes the FORMAT field more readable and reduces file sizes for large cohorts.

boolean  false

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--enable-all-annotations / NA

Use all possible annotations (not for the faint of heart)
You can use the -AX argument in combination with this one to exclude specific annotations. Note that some annotations may not be actually applied if they are not applicable to the data provided or if they are unavailable to the tool (e.g. there are several annotations that are currently not hooked up to HaplotypeCaller). At present no error or warning message will be provided, the annotation will simply be skipped silently. You can check the output VCF header to see which annotations were activated and thus might be applied (although this does not guarantee that the annotation was applied to all records in the VCF, since some annotations have additional requirements, e.g. minimum number of samples or heterozygous sites only -- see the documentation for individual annotations' requirements).

boolean  false

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--exclude-intervals / -XL

One or more genomic intervals to exclude from processing
Use this argument to exclude certain parts of the genome from the analysis (like -L, but the opposite). This argument can be specified multiple times. You can use samtools-style intervals either explicitly on the command line (e.g. -XL 1 or -XL 1:100-200) or by loading in a file containing a list of intervals (e.g. -XL myFile.intervals).

List[String]  []

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--founder-id / -founder-id

Samples representing the population "founders"

List[String]  []

---

--gatk-config-file / NA

A configuration file to use with the GATK.

String  null

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--gcs-max-retries / -gcs-retries

If the GCS bucket channel errors out, how many times it will attempt to re-initiate the connection

int  20  [ [ -∞  ∞ ] ]

---

--gcs-project-for-requester-pays / NA

Project to bill when accessing "requester pays" buckets. If unset, these buckets cannot be accessed.

String  ""

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--help / -h

display the help message

boolean  false

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--ignore-variants-starting-outside-interval / NA

Restrict variant output to sites that start within provided intervals (only applies when an interval is specified)
this option has no effect unless intervals are specified.

This exists to mimic GATK3 interval traversal patterns

boolean  false

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--input / -I

BAM/SAM/CRAM file containing reads

List[String]  []

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--input-is-somatic / NA

Merge input GVCFs according to somatic (i.e. Mutect2) annotations (BETA)
Merge somatic GVCFs, retaining LOD and haplotype event count information in FORMAT field Note that the Mutect2 reference confidence mode is in BETA -- the likelihoods model and output format are subject to change in subsequent versions.

boolean  false

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--interval-exclusion-padding / -ixp

Amount of padding (in bp) to add to each interval you are excluding.
Use this to add padding to the intervals specified using -XL. For example, '-XL 1:100' with a padding value of 20 would turn into '-XL 1:80-120'. This is typically used to add padding around targets when analyzing exomes.

int  0  [ [ -∞  ∞ ] ]

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--interval-merging-rule / -imr

Interval merging rule for abutting intervals
By default, the program merges abutting intervals (i.e. intervals that are directly side-by-side but do not actually overlap) into a single continuous interval. However you can change this behavior if you want them to be treated as separate intervals instead.

The --interval-merging-rule argument is an enumerated type (IntervalMergingRule), which can have one of the following values:

ALL

OVERLAPPING_ONLY

IntervalMergingRule  ALL

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--interval-padding / -ip

Amount of padding (in bp) to add to each interval you are including.
Use this to add padding to the intervals specified using -L. For example, '-L 1:100' with a padding value of 20 would turn into '-L 1:80-120'. This is typically used to add padding around targets when analyzing exomes.

int  0  [ [ -∞  ∞ ] ]

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--interval-set-rule / -isr

Set merging approach to use for combining interval inputs
By default, the program will take the UNION of all intervals specified using -L and/or -XL. However, you can change this setting for -L, for example if you want to take the INTERSECTION of the sets instead. E.g. to perform the analysis only on chromosome 1 exomes, you could specify -L exomes.intervals -L 1 --interval-set-rule INTERSECTION. However, it is not possible to modify the merging approach for intervals passed using -XL (they will always be merged using UNION). Note that if you specify both -L and -XL, the -XL interval set will be subtracted from the -L interval set.

The --interval-set-rule argument is an enumerated type (IntervalSetRule), which can have one of the following values:

UNION

Take the union of all intervals

INTERSECTION

Take the intersection of intervals (the subset that overlaps all intervals specified)

IntervalSetRule  UNION

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--intervals / -L

One or more genomic intervals over which to operate

List[String]  []

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--lenient / -LE

Lenient processing of VCF files

boolean  false

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--max-distance / NA

Maximum distance for variants to be grouped together

int  2147483647  [ [ -∞  ∞ ] ]

---

--output / -O

The combined GVCF output file

R File  null

---

--pedigree / -ped

Pedigree file for determining the population "founders"

File  null

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--QUIET / NA

Whether to suppress job-summary info on System.err.

Boolean  false

---

--read-filter / -RF

Read filters to be applied before analysis

List[String]  []

---

--read-index / -read-index

Indices to use for the read inputs. If specified, an index must be provided for every read input and in the same order as the read inputs. If this argument is not specified, the path to the index for each input will be inferred automatically.

List[String]  []

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--read-validation-stringency / -VS

Validation stringency for all SAM/BAM/CRAM/SRA files read by this program. The default stringency value SILENT can improve performance when processing a BAM file in which variable-length data (read, qualities, tags) do not otherwise need to be decoded.

The --read-validation-stringency argument is an enumerated type (ValidationStringency), which can have one of the following values:

STRICT

LENIENT

SILENT

ValidationStringency  SILENT

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--ref-padding / NA

Number of bases on either side to expand spanning reference window

int  1  [ [ -∞  ∞ ] ]

---

--reference / -R

Reference sequence file

R String  null

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--seconds-between-progress-updates / -seconds-between-progress-updates

Output traversal statistics every time this many seconds elapse

double  10.0  [ [ -∞  ∞ ] ]

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--sequence-dictionary / -sequence-dictionary

Use the given sequence dictionary as the master/canonical sequence dictionary. Must be a .dict file.

String  null

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--showHidden / -showHidden

display hidden arguments

boolean  false

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--sites-only-vcf-output / NA

If true, don't emit genotype fields when writing vcf file output.

boolean  false

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--tmp-dir / NA

Temp directory to use.

GATKPathSpecifier  null

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--use-jdk-deflater / -jdk-deflater

Whether to use the JdkDeflater (as opposed to IntelDeflater)

boolean  false

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--use-jdk-inflater / -jdk-inflater

Whether to use the JdkInflater (as opposed to IntelInflater)

boolean  false

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--variant / -V

One or more VCF files containing variants

R List[String]  []

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--verbosity / -verbosity

Control verbosity of logging.

The --verbosity argument is an enumerated type (LogLevel), which can have one of the following values:

ERROR

WARNING

INFO

DEBUG

LogLevel  INFO

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--version / NA

display the version number for this tool

boolean  false

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GATK version 4.1.6.0-SNAPSHOT built at Thu, 2 Apr 2020 14:54:17 -0400.