In silico assessment of CFTR: c.۱۱۱۸A>G (p.Asp۳۷۳Gly), a novel variant detected among Iranian population

Recent advances in genome sequencing have led to the identification of large amounts of variants in humangenes. As a national project, the Iranome project (http://www.iranome.ir/) was established recently in Iranand resulted in detecting many genomic variants not reported before. In this study, the effect of a variantdetected in cystic fibrosis transmembrane conductance regulator (CFTR) gene, c.۱۱۱۸A>G (p.Asp۳۷۳Gly),was investigated using ten in silico predictive tools including PhD- SNPg, PANTHER PSEP, SNPs & GO,FATHMM-XF, I-Mutant Disease, PolyPhen-۲, PROVEAN, Mutation Taster, CADD, and SIFT.NM_۰۰۰۴۹۲.۴ was used to determine the variant position and the position of the variant in protein wasdetermined based on UniProtKB/SwissProt P۱۳۵۶۹-۱. According to our results, except for PolyPhen-۲ andSNPs & GO, the other eight in silico tools predicted deleterious effects for this variant. CFTR: c.۱۱۱۸A>G(p.Asp۳۷۳Gly) variant had been detected in two healthy individuals with Persian ethnicity from Iran (both inheterozygous forms). Our efforts to find this variant in the literature were unsuccessful. In addition, it wasnot reported in LOVD, HGMD, dbSNP, ClinVar, gnomAD, ۱KGP, CFTR۱, and CFTR۲ public databases.In conclusion, with a threshold of deleterious effects in seven or more in silico predictive tools, CFTR:c.۱۱۱۸A>G (p.Asp۳۷۳Gly) variant could be accepted as a pathogenic variant. However, for its finalclassification, it is necessary to consider the other criteria provided by American College of Medical Geneticsand Genomics (ACMG-AMP) guidelines.

کلیدواژه ها:

Cystic fibrosis (CF) ، CFTR gene ، In silico analysis