15 March 2021

Ian Holmes has a twitter poll right now on the use of “SNP” (single-nucleotide polymorphism) versus “SNV” (single-nucleotide variant). I have been bugged by the two terminologies for years, so I decided to write a blog post on it. Personally, I use “SNP” for germline events and “SNV” for somatic events, but I understand others think differently. Here are my thoughts.

The wiki page for SNP defines a SNP as a nucleotide change “that is present in a sufficiently large fraction of the population (e.g. 1% or more)”. However, such a frequency-based definition is not actionable in practice. Allele frequency varies a lot across populations. Due to genetic drift and selection, an allele at 5% frequency in African may be absent from the rest of the world. Is this a SNP or not? Furthermore, the observed allele frequency fluctuates with sampling and the sample size. An allele at 2% frequency in the 1000 Genomes Project (1KG) may become 0.5% in gnomAD. Is this a SNP or not? If it is impractical to set a frequency threshold, the definition of SNP shouldn’t require a frequency threshold.

Historically, we have been using “SNP” without a frequency threshold for decades. If you search word “SNP” in the landmark paper on the Human Genome Project in 2001, you can find 45 instances. With data produced at that time, we had little information on frequency but we called observed substituions as SNPs anyway. Similarly, there are 28 instances of “SNP” in the final 1KG paper, including one in the abstract. In 1KG, we have observed many substitutions at <1% but we still called them as SNPs. In these papers, a SNP simply refers to a germline substitution.

“SNV” is a much more recent terminology. I first saw “SNV” in the SNVmix paper in the context of tumor mutation calling (I reviewed it). That was 2010. According to a PubMed search, few papers were published with “SNV” in the abstract before that and early uses of “SNV” mostly focused on tumor data as well. This includes the popular VarScan2 paper. People coined up “SNV” for somatic mutations because SNP has been reserved for germline events. “SNV” may sound more general than “SNP”, but concepts in genetics should not be taken literally. What matters more is the historical uses. There are simiarly confusing terminologies like VNTR and CNV vs CNA, which I will not explain in detail here.

It is already too late to regulate the use of SNP and SNV. In practice, just beware that the definition of SNP and SNV may vary between researchers. When in a conversation you are not sure what SNP/SNV refers to, ask for a clarification.

Postscript: I personally avoid “SNV” in my work due to its inconsistent uses in the past. When I want to describe a somatic event, I use “somatic SNV” or “sSNV” in brief.

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