Variant Call Format

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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 4.2,[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[edit]

##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[edit]

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[edit]

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.

Name Brief description (see the specification for details).
1 CHROM The name of the sequence (typically a chromosome) on which the variation is being called. This sequence is usually known as 'the reference sequence', i.e. the sequence against which the given sample varies.
2 POS The 1-based position of the variation on the given sequence.
3 ID The identifier of the variation, e.g. a dbSNP rs identifier or just . if unknown. Multiple identifiers should be separated by semi-colons without white-space.
4 REF The reference base (or bases in the case of an InDel at the given position on the given reference sequence.
5 ALT The list of alternative alleles at this position.
6 QUAL A quality score associated with the inference of the given alleles.
7 FILTER A flag indicating which of a given set of filters the variation has passed.
8 INFO An extensible list of key-value pairs (fields) describing the variation. See below for some common fields. Multiple fields are separated by semicolons with optional values in the format: "<key>=[,data]".
9 FORMAT An (optional) extensible list of fields for describing the samples. See below for some common fields.
+ SAMPLEs For each (optional) sample described in the file, values are given for the fields listed in FORMAT

Common INFO fields[edit]

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[edit]

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[edit]

References[edit]