Variant nomenclature must be standardized for robust computational analysis of variants and interoperability between databases. Over the last decade or so, the community has widely adopted the standards of the Human Genome Variation Society (HGVS) [19, 103]. Previous to that, there were multiple mutually inconsistent ways of numbering nucleotides and denoting various classes of variant. For example, in an early publication from the year 1997 by one of the authors of this book, a mutation in the fibrillin-1 gene was denoted as G1760A . Hopefully it was clear to the readers of the publication from the context that G1760A referred to a change of the nucleotide sequence, an exchange of a guanine for an adenosine base at position 1760 of the coding sequence. But in principle, G1760A could also refer to an exchange of a glycine residue for an alanine residue at position 1760 of a protein. The HGVS recommendations intend to supply unambiguous, precise descriptions of genetic variants, and are today nearly universally used. This chapter explains the basics of the HGVS nomenclature, and then shows how it is used to describe the various classes of variant that are encountered in WES and WGS data.