Mutation and variant

A variant is any difference from the reference sequence: a single base swap (SNV), a small insertion or deletion (indel) or a larger change in copy number. In coding regions a base swap can stay silent, change an amino acid or set a stop signal. Variant is the neutral word; mutation often sounds rare or harmful.

VARIANTS · TYPES AND EFFECT SNVone letter ACATA base G → A Indelinsert or delete ACTA G +1 base inserted CNVcopy number section multiplied In a coding region an SNV acts like this: synonymousGCU → GCCsame amino acid missenseGCU → GUUAla → Val nonsenseCAA → UAAearly stop

The types of variants

Smallest is the single-base variant, an SNV: one letter is swapped for another. An indel inserts or removes a few bases and can shift the reading frame. Larger still are copy-number variants (CNV), where whole sections are missing or present multiple times. The range spans from one letter to millions of bases.

Effect in the coding region

If an SNV hits an exon, the genetic code decides the consequence. Synonymous: the same codon result, the amino acid stays. Missense: a different amino acid, the effect depends on the spot in the protein. Nonsense: a stop codon arises and the protein breaks off. A frameshift from an indel can render the entire text behind it useless.

Variant, polymorphism, mutation

The terms overlap. A common variant present in more than one percent of people is called a polymorphism, in the case of a single base an SNP. Mutation rather stresses new occurrence or a disease link. Technically, variants are classified from benign to pathogenic by fixed criteria. The vast majority are benign.

What Genome measures. Genome reads mostly SNVs at known positions. The result names which base you carry; the article says what the change means at that spot.

Related topics

DNA: bases and double helixThe genetic codeGene structure: exon, intron, promoterrsIDs, microarray and SNP lookupDisease associations

Sources

  1. 1Richards et al., 2015 Standards and guidelines for the interpretation of sequence variants (ACMG/AMP). Genetics in Medicine 17:405–424. doi.org/10.1038/gim.2015.30
  2. 2Karczewski et al., 2020 The mutational constraint spectrum quantified from variation in 141,456 humans (gnomAD). Nature 581:434–443. doi.org/10.1038/s41586-020-2308-7