Background: The variant call format (VCF) is currently used to store information on genetic variants. Variant description from the VCF is not unique or standardized. A recent survey indicated that more than half of the clinical laboratories in Korea have not performed VCF normalization procedures in their bioinformatics pipeline during routine analysis. We evaluated the effect of variant normalization on variant nomenclature using two tools.
Methods: Two binary alignment map files (GNG-21-01 and GNG-21-04) and validated variant descriptions (single-nucleotide variations [n=51] and insertions/duplications/deletions [n=13]) were provided by the Korean Association of External Quality Assessment Service. Variant calling and annotation were performed using Torrent Suite and snpEff, respectively. The vt-normalize and Genome Analysis Toolkit (GATK) LeftAlignAndTrimVariants (LAATV) were used to evaluate the effect of VCF normalization.
Results: The accuracy of the nomenclature of un-normalized variants was 99% (63/64); one variant of NM_173630.3(RTTN): c.725_727dupGAG was incorrectly described as c.724_726dupGGA. The variant description was corrected through VCF normalization. The normalization results obtained using vt-normalize and GATK LAATV were comparable.
Conclusions: VCF normalization may not generate completely correct nomenclature but contributes to more accurate annotation of variants. VCF normalization should be introduced into bioinformatics pipelines in clinical laboratories to ensure more reliable annotations of variants.

Keywords: Variant call format, Variant, Normalization, Nomenclature