ClinVar

Description

IFIH1 NM_022168.3 exon 8 c.1641+1G>C: This variant has not been reported in the literature in association with traditional Mendelian disease, but has been reported as heterozygous in 3 healthy children who were hospitalized due to viral infection (Asgari 2017 PMID:28716935). This variant is present in 1% (1362/125804) of European alleles, including 7 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-163136505-C-G). This variant is present in ClinVar (Variation ID:261563) with at least 2 labs classifying this variant as Benign. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. However, there is limited evidence for this gene and to support loss of function (LOF) as a known disease mechanism. In vitro functional studies suggest that this variant will impact the protein by causing an in-frame loss of 39 amino acids and the skipping of exon 8; thus potentially disrupting signaling function, enzymatic activity and protein stability (Asgari 2017 PMID:28716935). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.