1st International and 10th National Iranian Conference on Bioinformatics

In silico assessment of CFTR: c.1118A>G (p.Asp373Gly), a novel variant detected among Iranian population

Paper ID : 1036-ICB10

Authors:

Keivan Moradi *, Sahand Khamooshian

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract:

Recent advances in genome sequencing have led to the identification of large amounts of variants in human genes. As a national project, the Iranome project (http://www.iranome.ir/) was established recently in Iran and resulted in detecting many genomic variants not reported before. In this study, the effect of a variant detected in cystic fibrosis transmembrane conductance regulator (CFTR) gene, c.1118A>G (p.Asp373Gly), was investigated using ten in silico predictive tools including PhD- SNPg, PANTHER PSEP, SNPs & GO, FATHMM-XF, I-Mutant Disease, PolyPhen-2, PROVEAN, Mutation Taster, CADD, and SIFT. NM_000492.4 was used to determine the variant position and the position of the variant in protein was determined based on UniProtKB/SwissProt P13569-1. According to our results, except for PolyPhen-2 and SNPs & GO, the other eight in silico tools predicted deleterious effects for this variant. CFTR: c.1118A>G (p.Asp373Gly) variant had been detected in two healthy individuals with Persian ethnicity from Iran (both in heterozygous forms). Our efforts to find this variant in the literature were unsuccessful. In addition, it was not reported in LOVD, HGMD, dbSNP, ClinVar, gnomAD, 1KGP, CFTR1, and CFTR2 public databases. In conclusion, with a threshold of deleterious effects in seven or more in silico predictive tools, CFTR: c.1118A>G (p.Asp373Gly) variant could be accepted as a pathogenic variant. However, for its final classification, it is necessary to consider the other criteria provided by American College of Medical Genetics and Genomics (ACMG-AMP) guidelines.

Keywords:

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

Status : Paper Accepted (Poster Presentation)