Variant Call Format

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Variant Call Format
Filename extension
.vcf
Developed by1000 Genomes Project
Latest release
4.3
January 13, 2021; 3 years ago (2021-01-13)
Type of formatBioinformatics
Extended fromTab-separated values
Extended togVCF
Open format?Yes
Websitesamtools.github.io/hts-specs/VCFv4.3.pdf

The Variant Call Format (VCF) is a standard text file format used in

gene sequence variations. The format was developed in 2010 for the 1000 Genomes Project and has since been used by other large-scale genotyping and DNA sequencing projects.[1][2] VCF is a common output format for variant calling programs due to its relative simplicity and scalability.[3][4] Many tools have been developed for editing and manipulating VCF files, including VCFtools, which was released in conjunction with the VCF format in 2011, and BCFtools, which was included as part of SAMtools until being split into an independent package in 2014.[1][5]

The standard is currently in version 4.3,[6][7] although the 1000 Genomes Project has developed its own specification for structural variations such as duplications, which are not easily accommodated into the existing schema.[8]

Additional file formats have been developed based on VCF, including genomic VCF (gVCF). gVCF is an extended format which includes additional information about "blocks" that match the reference and their qualities.[9][10]

Example

##fileformat=VCFv4.3
##fileDate=20090805
##source=myImputationProgramV3.1
##reference=file:///seq/references/1000GenomesPilot-NCBI36.fasta
##contig=<ID=20,length=62435964,assembly=B36,md5=f126cdf8a6e0c7f379d618ff66beb2da,species="Homo sapiens",taxonomy=x>
##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=A,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=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=GQ,Number=1,Type=Integer,Description="Genotype Quality">
##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       NA00001         NA00002          NA00003
20     14370    rs6054257  G     A      29    PASS    NS=3;DP=14;AF=0.5;DB;H2           GT:GQ:DP:HQ  0|0:48:1:51,51  1|0:48:8:51,51   1/1:43:5:.,.
20     17330    .          T     A      3     q10     NS=3;DP=11;AF=0.017               GT:GQ:DP:HQ  0|0:49:3:58,50  0|1:3:5:65,3     0/0:41:3
20     1110696  rs6040355  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
20     1230237  .          T     .      47    PASS    NS=3;DP=13;AA=T                   GT:GQ:DP:HQ  0|0:54:7:56,60  0|0:48:4:51,51   0/0:61:2
20     1234567  microsat1  GTC   G,GTCT 50    PASS    NS=3;DP=9;AA=G                    GT:GQ:DP     0/1:35:4        0/2:17:2         1/1:40:3
BCF v VCF
Demonstrating the difference between the binary BCF and VCF formats.

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 columns of a VCF

The body of VCF follows the header, and is tab separated into 8 mandatory columns and an unlimited number of optional columns that may be used to record other information about the sample(s). When additional columns are used, the first optional column is used to describe the format of the data in the columns that follow.

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 if unknown a ".". 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 failed or PASS if all the filters were passed successfully.
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>[,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

Arbitrary keys are permitted, although the following sub-fields are reserved (albeit optional):[6]

Name Brief description
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

Any other info fields are defined in the .vcf header.

Common FORMAT fields

Name Brief description
AD Read depth for each allele
ADF Read depth for each allele on the forward strand
ADR Read depth for each allele on the reverse strand
DP Read depth
EC Expected alternate allele counts
FT Filter indicating if this genotype was “called”
GL Genotype likelihoods
GP Genotype posterior probabilities
GQ Conditional genotype quality
GT Genotype
HQ Haplotype quality
MQ RMS mapping quality
PL Phred-scaled genotype likelihoods rounded to the closest integer
PQ Phasing quality
PS Phase set

Any other format fields are defined in the .vcf header.

See also

  • The FASTA format, used to represent genome sequences.
  • The FASTQ format, used to represent DNA sequencer reads along with quality scores.
  • The SAM format, used to represent genome sequencer reads that have been aligned to genome sequences.
  • The
    GFF3
    format.
  • Global Alliance for Genomics and Health (GA4GH), the group leading the management and expansion of the VCF format.[11] The VCF specification is no longer maintained by the 1000 Genomes Project.[12]

References

  1. ^
    PMID 21653522
    .
  2. ^ Ossola, Alexandra (20 March 2015). "The Race to Build a Search Engine for Your DNA". IEEE Spectrum. Retrieved 22 March 2015.
  3. EMBL-EBI. Archived
    from the original on 2023-04-20. Retrieved 2023-11-10.
  4. PMID 35639788
    .
  5. PMID 33590861
    .
  6. ^ a b "VCF Specification" (PDF). Retrieved 20 Oct 2016.
  7. ^ "Specifications of SAM/BAM and related high-throughput sequencing file formats". GitHub. Retrieved 24 June 2014.
  8. ^ "Encoding Structural Variants in VCF (Variant Call Format) version 4.0 | 1000 Genomes". Retrieved 20 October 2016.
  9. ^ "GVCF - Genomic Variant Call Format". GATK. Broad Institute.
  10. ^ "gVCF Files". Illumina, Inc. Retrieved 2023-11-10.
  11. ^ "HTS format specifications". samtools.github.io. Retrieved 2022-02-22.
  12. ^ "Bio-IT World". www.bio-itworld.com. Retrieved 2018-10-26.

External links

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