What is a VCF file?

A VCF file (Variant Call Format) is a tab-delimited text format that records genomic variant sites, the alleles observed at each site, and (optionally) per-sample genotypes and supporting metrics.

Why VCF files exist

Sequencing reads are aligned to a reference genome, then variant calling identifies positions where one or more samples differ from that reference. VCF is the standard way to publish those variant calls so they can be compared, annotated, interpreted, and exchanged between tools.

Minimal structure of a VCF

A VCF has two parts:

• Header lines beginning with ##, which define metadata and the meaning of annotations.
• A single column header line beginning with #CHROM, followed by one record per site.

Each record has eight required site columns, then optional genotype columns:

A “sites-only” VCF may stop at INFO and omit FORMAT and sample columns.

Example record explained

Example:

#CHROM POS ID REF ALT QUAL FILTER INFO    FORMAT  SAMPLE1
20     10001617 .  C   A   493.77 PASS   DP=38   GT:DP   0/1:38

Explanation:

• CHROM=20, POS=10001617: the site location.
• ID=.: no identifier provided.
• REF=C, ALT=A: the reference base is C, and an alternate allele A is observed. If there were multiple alternates they would appear as ALT=A,T and are indexed in that order.
• QUAL=493.77: a site confidence value produced by the caller (the scale is caller-defined).
• FILTER=PASS: this record passed filters. A value of . means no filtering was applied.
• INFO=DP=38: a site annotation. INFO/DP commonly represents read depth at the site, but the precise definition is caller-specific.

FORMAT defines the schema for each sample column:

• FORMAT=GT:DP means the sample column contains two fields, genotype then depth, separated by :.

The sample value is:

• GT=0/1: allele indices. 0 means REF. 1 means the first allele in ALT.
  • 0/0 is homozygous reference.
  • 0/1 is heterozygous.
  • 1/1 is homozygous alternate.
  • / indicates unphased genotypes. | indicates phased genotypes (for example 0|1).
  • Missing values are written as . (for example ./.).
• DP=38: per-sample depth for this site as defined by the caller. This is separate from INFO/DP, and may differ in meaning and value depending on the calling method and filters.

Representation details that matter

• Indels include an anchoring base: insertions and deletions are represented with REF and ALT strings that include a shared left-side base, so POS points to that anchor. This is why deletions often appear to be reported at the base before the deleted stretch.
• Multiallelic sites: if ALT has multiple alleles, genotypes use indices beyond 1 (for example 2/2 refers to the second listed ALT allele).
• Header definitions: the intended meaning of INFO and FORMAT tags is declared in header lines such as ##INFO=<ID=DP,...> and ##FORMAT=<ID=GT,...>.

Where VCF fits in pipelines

Typical workflow:

Sequencing → Alignment (BAM/CRAM) → Variant calling → VCF → Annotation and interpretation

VCF vs gVCF

A VCF usually records variant sites only. A gVCF is designed for joint genotyping and also represents non-variant regions, typically by emitting reference-confidence information and sometimes compressing non-variant stretches into blocks.

Relation to Switzerland Omics systems

Switzerland Omics systems consume VCF-derived variant and genotype evidence during evidence extraction, probabilistic interpretation, and structured reporting.

Technical specification

For the authoritative specification, see the VCF definition in the hts-specs repository: https://samtools.github.io/hts-specs/