What Is VAF (Variant Allele Frequency)

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∟What Is VAF (Variant Allele Frequency)

Provides a quick introduction of VAF (Variant Allele Frequency), which is defined as the ratio of variant reads over read depth using NGS (Next-Generation Sequencing) terminologies.

In previous tutorials, Allele Frequency is used as a term to estimate how frequent a specific allele type (DNA alternation, or mutation) appears in a population of individuals.

Now, let's look at a related term, Variant Allele Frequency, used in NGS (Next Generation Sequencing) analysis.

What Is Variant Allele Frequency (VAF)? - VAF is the ratio of the variant reads over read depth, using terminologies from the NGS technology. VAF is used to estimate how frequent a specific allele type (DNA alternation, or mutation) appear in the entire body, or certain part of the body, of a single individual.

VAF can be written more formally as:

VAF = AD / DP

Where:
  DP, Read Depth or Coverage:
     Total umber of reads at the given location.

  AD (Allele Depth), or variant reads, or Variant read number:
    Number of reads that contains this variant at the given location.

In theory, a homozygous variant should have 100% VAF, because both chromosome sequences in the chromosome pair carry the variant. And a heterozygous variant should have 50% VAF, because only 1 chromosome sequence in the chromosome pair carries the variant.

If a variant has 25% VAF, and the sample is tumor issue, then this variant could be a variant in tumor cells only, and sample is mixed with 50% tumor cells and normal cells. In this case, the variant is heterozygous and exist in 50% genome sequences (half of the chromosome pair) of 50% cells (tumor cells only), resulting 50% * 50% = 25% VAF.