Variant Call Format

The Variant Call Format (VCF) specifies the format of a text file used in bioinformatics for storing gene sequence variations. The format has been developed with the advent of large-scale genotyping and DNA sequencing projects, such as the 1000 Genomes Project. Existing formats for genetic data such as General feature format (GFF) stored all of the genetic data, much of which is redundant because it will be shared across the genomes. By using the variant call format only the variations need to be stored along with a reference genome.

The standard is currently in version 4.3,^[1][2] although the 1000 Genomes Project has developed their own specification for structural variations such as duplications, which are not easily accommodated into the existing schema.^[3] A set of tools is also available for editing and manipulating the files.^[4]

Example

##fileformat=VCFv4.0
##fileDate=20110705
##reference=1000GenomesPilot-NCBI37
##phasing=partial
##INFO=<ID=NS,Number=1,Type=Integer,Description="Number of Samples With Data">
##INFO=<ID=DP,Number=1,Type=Integer,Description="Total Depth">
##INFO=<ID=AF,Number=.,Type=Float,Description="Allele Frequency">
##INFO=<ID=AA,Number=1,Type=String,Description="Ancestral Allele">
##INFO=<ID=DB,Number=0,Type=Flag,Description="dbSNP membership, build 129">
##INFO=<ID=H2,Number=0,Type=Flag,Description="HapMap2 membership">
##FILTER=<ID=q10,Description="Quality below 10">
##FILTER=<ID=s50,Description="Less than 50% of samples have data">
##FORMAT=<ID=GQ,Number=1,Type=Integer,Description="Genotype Quality">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
##FORMAT=<ID=HQ,Number=2,Type=Integer,Description="Haplotype Quality">
#CHROM POS    ID        REF  ALT     QUAL FILTER INFO                              FORMAT      Sample1        Sample2        Sample3
2      4370   rs6057    G    A       29   .      NS=2;DP=13;AF=0.5;DB;H2           GT:GQ:DP:HQ 0|0:48:1:52,51 1|0:48:8:51,51 1/1:43:5:.,.
2      7330   .         T    A       3    q10    NS=5;DP=12;AF=0.017               GT:GQ:DP:HQ 0|0:46:3:58,50 0|1:3:5:65,3   0/0:41:3
2      110696 rs6055    A    G,T     67   PASS   NS=2;DP=10;AF=0.333,0.667;AA=T;DB GT:GQ:DP:HQ 1|2:21:6:23,27 2|1:2:0:18,2   2/2:35:4
2      130237 .         T    .       47   .      NS=2;DP=16;AA=T                   GT:GQ:DP:HQ 0|0:54:7:56,60 0|0:48:4:56,51 0/0:61:2
2      134567 microsat1 GTCT G,GTACT 50   PASS   NS=2;DP=9;AA=G                    GT:GQ:DP    0/1:35:4       0/2:17:2       1/1:40:3
chr1	45796269	.	G	C
chr1	45797505	.	C	G
chr1	45798555	.	T	C
chr1	45798901	.	C	T
chr1	45805566	.	G	C
chr2	47703379	.	C	T
chr2	48010488	.	G	A
chr2	48030838	.	A	T
chr2	48032875	.	CTAT	-
chr2	48032937	.	T	C
chr2	48033273	.	TTTTTGTTTTAATTCCT	-
chr2	48033551	.	C	G
chr2	48033910	.	A	T
chr2	215632048	.	G	T
chr2	215632125	.	TT	-
chr2	215632155	.	T	C
chr2	215632192	.	G	A
chr2	215632255	.	CA	TG
chr2	215634055	.	C	T

The VCF header

The header begins the file and provides metadata describing the body of the file. Header lines are denoted as starting with #. Special keywords in the header are denoted with ##. Recommended keywords include fileformat, fileDate and reference.

The header contains keywords that optionally semantically and syntactically describe the fields used in the body of the file, notably INFO, FILTER, and FORMAT (see below).

The nine columns of VCF

The body of VCF follows the header, and is tab separated into eight columns. An unlimited number of further columns give optional information about samples.

Common INFO fields

Arbitrary keys are permitted, although the following sub-fields are reserved (albeit optional):

AA 

ancestral allele

AC 

allele count in genotypes, for each ALT allele, in the same order as listed

AF 

allele frequency for each ALT allele in the same order as listed: use this when estimated from primary data, not called genotypes

AN 

total number of alleles in called genotypes

BQ 

RMS base quality at this position

CIGAR 

cigar string describing how to align an alternate allele to the reference allele

DB 

dbSNP membership

DP 

combined depth across samples, e.g. DP=154

END 

end position of the variant described in this record (for use with symbolic alleles)

H2 

membership in hapmap2

H3 

membership in hapmap3

MQ 

RMS mapping quality, e.g. MQ=52

MQ0 

Number of MAPQ == 0 reads covering this record

NS 

Number of samples with data

SB 

strand bias at this position

SOMATIC 

indicates that the record is a somatic mutation, for cancer genomics

VALIDATED 

validated by follow-up experiment

1000G 

membership in 1000 Genomes

See also

• The Genome Variation Format (GVF), an extension based on the GFF3 format.

The VCF specification is no longer maintained by the 1000 Genomes Project. The group leading the management and expansion of the format is the Global Alliance for Genomics and Health Data Working group file format team, http://ga4gh.org/#/fileformats-team

External links

• An explanation of the format in picture form
• Free, graphical tool to inspect, search, split and merge VCF files on OS X
• Ossola, Alexandra (20 March 2015). "The Race to Build a Search Engine for Your DNA". IEEE Spectrum. Retrieved March 2015.  Check date values in: |access-date= (help)

References