Overview
GVCF stands for Genomic VCF. A GVCF is a kind of VCF, so the basic format specification is the same as for a regular VCF (see the spec documentation here), but a Genomic VCF contains extra information.
This document explains what that extra information is and how you can use it to empower your variants analyses.
Important caveat
What we're covering here is strictly limited to GVCFs produced by HaplotypeCaller in GATK versions 3.0 and above. The term GVCF is sometimes used simply to describe VCFs that contain a record for every position in the genome (or interval of interest) regardless of whether a variant was detected at that site or not (such as VCFs produced by UnifiedGenotyper with --output_mode EMIT_ALL_SITES). GVCFs produced by HaplotypeCaller 3.x contain additional information that is formatted in a very specific way. Read on to find out more.
General comparison of VCF vs. gVCF
The key difference between a regular VCF and a gVCF is that the gVCF has records for all sites, whether there is a variant call there or not. The goal is to have every site represented in the file in order to do joint analysis of a cohort in subsequent steps. The records in a gVCF include an accurate estimation of how confident we are in the determination that the sites are homozygous-reference or not. This estimation is generated by the HaplotypeCaller's built-in reference model.
Note that some other tools (including the GATK's own UnifiedGenotyper) may output an all-sites VCF that looks superficially like the BP_RESOLUTION gVCFs produced by HaplotypeCaller, but they do not provide an accurate estimate of reference confidence, and therefore cannot be used in joint genotyping analyses.
The two types of gVCFs
As you can see in the figure above, there are two options you can use with -ERC: GVCF and BP_RESOLUTION. With BP_RESOLUTION, you get a gVCF with an individual record at every site: either a variant record, or a non-variant record. With GVCF, you get a gVCF with individual variant records for variant sites, but the non-variant sites are grouped together into non-variant block records that represent intervals of sites for which the genotype quality (GQ) is within a certain range or band. The GQ ranges are defined in the ##GVCFBlock line of the gVCF header. The purpose of the blocks (also called banding) is to keep file size down, and there is no downside for the downstream analysis, so we do recommend using the -GVCF option.
Example gVCF file
This is a banded gVCF produced by HaplotypeCaller with the -GVCF option.
Header:
As you can see in the first line, the basic file format is a valid version 4.1 VCF:
##fileformat=VCFv4.1
##ALT=<ID=NON_REF,Description="Represents any possible alternative allele at this location">
##FILTER=<ID=LowQual,Description="Low quality">
##FORMAT=<ID=AD,Number=.,Type=Integer,Description="Allelic depths for the ref and alt alleles in the order listed">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Approximate read depth (reads with MQ=255 or with bad mates are filtered)">
##FORMAT=<ID=GQ,Number=1,Type=Integer,Description="Genotype Quality">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=MIN_DP,Number=1,Type=Integer,Description="Minimum DP observed within the GVCF block">
##FORMAT=<ID=PL,Number=G,Type=Integer,Description="Normalized, Phred-scaled likelihoods for genotypes as defined in the VCF specification">
##FORMAT=<ID=SB,Number=4,Type=Integer,Description="Per-sample component statistics which comprise the Fisher's Exact Test to detect strand bias.">
##GVCFBlock=minGQ=0(inclusive),maxGQ=5(exclusive)
##GVCFBlock=minGQ=20(inclusive),maxGQ=60(exclusive)
##GVCFBlock=minGQ=5(inclusive),maxGQ=20(exclusive)
##GVCFBlock=minGQ=60(inclusive),maxGQ=2147483647(exclusive)
##INFO=<ID=BaseQRankSum,Number=1,Type=Float,Description="Z-score from Wilcoxon rank sum test of Alt Vs. Ref base qualities">
##INFO=<ID=ClippingRankSum,Number=1,Type=Float,Description="Z-score From Wilcoxon rank sum test of Alt vs. Ref number of hard clipped bases">
##INFO=<ID=DP,Number=1,Type=Integer,Description="Approximate read depth; some reads may have been filtered">
##INFO=<ID=DS,Number=0,Type=Flag,Description="Were any of the samples downsampled?">
##INFO=<ID=END,Number=1,Type=Integer,Description="Stop position of the interval">
##INFO=<ID=HaplotypeScore,Number=1,Type=Float,Description="Consistency of the site with at most two segregating haplotypes">
##INFO=<ID=InbreedingCoeff,Number=1,Type=Float,Description="Inbreeding coefficient as estimated from the genotype likelihoods per-sample when compared against the Hardy-Weinberg expectation">
##INFO=<ID=MLEAC,Number=A,Type=Integer,Description="Maximum likelihood expectation (MLE) for the allele counts (not necessarily the same as the AC), for each ALT allele, in the same order as listed">
##INFO=<ID=MLEAF,Number=A,Type=Float,Description="Maximum likelihood expectation (MLE) for the allele frequency (not necessarily the same as the AF), for each ALT allele, in the same order as listed">
##INFO=<ID=MQ,Number=1,Type=Float,Description="RMS Mapping Quality">
##INFO=<ID=MQ0,Number=1,Type=Integer,Description="Total Mapping Quality Zero Reads">
##INFO=<ID=MQRankSum,Number=1,Type=Float,Description="Z-score From Wilcoxon rank sum test of Alt vs. Ref read mapping qualities">
##INFO=<ID=ReadPosRankSum,Number=1,Type=Float,Description="Z-score from Wilcoxon rank sum test of Alt vs. Ref read position bias">
##contig=<ID=20,length=63025520,assembly=b37>
##reference=file:///humgen/1kg/reference/human_g1k_v37.fasta
Toward the middle you see the ##GVCFBlock lines (after the ##FORMAT lines) (repeated here for clarity):
##GVCFBlock=minGQ=0(inclusive),maxGQ=5(exclusive)
##GVCFBlock=minGQ=20(inclusive),maxGQ=60(exclusive)
##GVCFBlock=minGQ=5(inclusive),maxGQ=20(exclusive)
which indicate the GQ ranges used for banding (corresponding to the boundaries [5, 20, 60]).
You can also see the definition of the MIN_DP annotation in the ##FORMAT lines.
Records
The first thing you'll notice, hopefully, is the <NON_REF> symbolic allele listed in every record's ALT field. This provides us with a way to represent the possibility of having a non-reference allele at this site, and to indicate our confidence either way.
The second thing to look for is the END tag in the INFO field of non-variant block records. This tells you at what position the block ends. For example, the first line is a non-variant block that starts at position 20:10000000 and ends at 20:10000116.
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT NA12878
20 10000000 . T <NON_REF> . . END=10000116 GT:DP:GQ:MIN_DP:PL 0/0:44:99:38:0,89,1385
20 10000117 . C T,<NON_REF> 612.77 . BaseQRankSum=0.000;ClippingRankSum=-0.411;DP=38;MLEAC=1,0;MLEAF=0.500,0.00;MQ=221.39;MQ0=0;MQRankSum=-2.172;ReadPosRankSum=-0.235 GT:AD:DP:GQ:PL:SB 0/1:17,21,0:38:99:641,0,456,691,519,1210:6,11,11,10
20 10000118 . T <NON_REF> . . END=10000210 GT:DP:GQ:MIN_DP:PL 0/0:42:99:38:0,80,1314
20 10000211 . C T,<NON_REF> 638.77 . BaseQRankSum=0.894;ClippingRankSum=-1.927;DP=42;MLEAC=1,0;MLEAF=0.500,0.00;MQ=221.89;MQ0=0;MQRankSum=-1.750;ReadPosRankSum=1.549 GT:AD:DP:GQ:PL:SB 0/1:20,22,0:42:99:667,0,566,728,632,1360:9,11,12,10
20 10000212 . A <NON_REF> . . END=10000438 GT:DP:GQ:MIN_DP:PL 0/0:52:99:42:0,99,1403
20 10000439 . T G,<NON_REF> 1737.77 . DP=57;MLEAC=2,0;MLEAF=1.00,0.00;MQ=221.41;MQ0=0 GT:AD:DP:GQ:PL:SB 1/1:0,56,0:56:99:1771,168,0,1771,168,1771:0,0,0,0
20 10000440 . T <NON_REF> . . END=10000597 GT:DP:GQ:MIN_DP:PL 0/0:56:99:49:0,120,1800
20 10000598 . T A,<NON_REF> 1754.77 . DP=54;MLEAC=2,0;MLEAF=1.00,0.00;MQ=185.55;MQ0=0 GT:AD:DP:GQ:PL:SB 1/1:0,53,0:53:99:1788,158,0,1788,158,1788:0,0,0,0
20 10000599 . T <NON_REF> . . END=10000693 GT:DP:GQ:MIN_DP:PL 0/0:51:99:47:0,120,1800
20 10000694 . G A,<NON_REF> 961.77 . BaseQRankSum=0.736;ClippingRankSum=-0.009;DP=54;MLEAC=1,0;MLEAF=0.500,0.00;MQ=106.92;MQ0=0;MQRankSum=0.482;ReadPosRankSum=1.537 GT:AD:DP:GQ:PL:SB 0/1:21,32,0:53:99:990,0,579,1053,675,1728:9,12,10,22
20 10000695 . G <NON_REF> . . END=10000757 GT:DP:GQ:MIN_DP:PL 0/0:48:99:45:0,120,1800
20 10000758 . T A,<NON_REF> 1663.77 . DP=51;MLEAC=2,0;MLEAF=1.00,0.00;MQ=59.32;MQ0=0 GT:AD:DP:GQ:PL:SB 1/1:0,50,0:50:99:1697,149,0,1697,149,1697:0,0,0,0
20 10000759 . A <NON_REF> . . END=10001018 GT:DP:GQ:MIN_DP:PL 0/0:40:99:28:0,65,1080
20 10001019 . T G,<NON_REF> 93.77 . BaseQRankSum=0.058;ClippingRankSum=-0.347;DP=26;MLEAC=1,0;MLEAF=0.500,0.00;MQ=29.65;MQ0=0;MQRankSum=-0.925;ReadPosRankSum=0.000 GT:AD:DP:GQ:PL:SB 0/1:19,7,0:26:99:122,0,494,179,515,694:12,7,4,3
20 10001020 . C <NON_REF> . . END=10001020 GT:DP:GQ:MIN_DP:PL 0/0:26:72:26:0,72,1080
20 10001021 . T <NON_REF> . . END=10001021 GT:DP:GQ:MIN_DP:PL 0/0:25:37:25:0,37,909
20 10001022 . C <NON_REF> . . END=10001297 GT:DP:GQ:MIN_DP:PL 0/0:30:87:25:0,72,831
20 10001298 . T A,<NON_REF> 1404.77 . DP=41;MLEAC=2,0;MLEAF=1.00,0.00;MQ=171.56;MQ0=0 GT:AD:DP:GQ:PL:SB 1/1:0,41,0:41:99:1438,123,0,1438,123,1438:0,0,0,0
20 10001299 . C <NON_REF> . . END=10001386 GT:DP:GQ:MIN_DP:PL 0/0:43:99:39:0,95,1226
20 10001387 . C <NON_REF> . . END=10001418 GT:DP:GQ:MIN_DP:PL 0/0:41:42:39:0,21,315
20 10001419 . T <NON_REF> . . END=10001425 GT:DP:GQ:MIN_DP:PL 0/0:45:12:42:0,9,135
20 10001426 . A <NON_REF> . . END=10001427 GT:DP:GQ:MIN_DP:PL 0/0:49:0:48:0,0,1282
20 10001428 . T <NON_REF> . . END=10001428 GT:DP:GQ:MIN_DP:PL 0/0:49:21:49:0,21,315
20 10001429 . G <NON_REF> . . END=10001429 GT:DP:GQ:MIN_DP:PL 0/0:47:18:47:0,18,270
20 10001430 . G <NON_REF> . . END=10001431 GT:DP:GQ:MIN_DP:PL 0/0:45:0:44:0,0,1121
20 10001432 . A <NON_REF> . . END=10001432 GT:DP:GQ:MIN_DP:PL 0/0:43:18:43:0,18,270
20 10001433 . T <NON_REF> . . END=10001433 GT:DP:GQ:MIN_DP:PL 0/0:44:0:44:0,0,1201
20 10001434 . G <NON_REF> . . END=10001434 GT:DP:GQ:MIN_DP:PL 0/0:44:18:44:0,18,270
20 10001435 . A <NON_REF> . . END=10001435 GT:DP:GQ:MIN_DP:PL 0/0:44:0:44:0,0,1130
20 10001436 . A AAGGCT,<NON_REF> 1845.73 . DP=43;MLEAC=2,0;MLEAF=1.00,0.00;MQ=220.07;MQ0=0 GT:AD:DP:GQ:PL:SB 1/1:0,42,0:42:99:1886,125,0,1888,126,1890:0,0,0,0
20 10001437 . A <NON_REF> . . END=10001437 GT:DP:GQ:MIN_DP:PL 0/0:44:0:44:0,0,0
Note that toward the end of this snippet, you see multiple consecutive non-variant block records. These were not merged into a single record because the sites they contain belong to different ranges of GQ (which are defined in the header).