ClinVar

Description

Variant summary: The c.417G>A variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 5/5 in silico tools via Alamut the gain of a cryptic splice acceptor site, however, the significance of these predictions has not been supported with functional studies. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.28%, predominantly observed in the East Asian subpopulation at a frequency of 1.9% including 2 homozygous occurrences. This frequency greatly exceeds the maximal expected allele frequency for a pathogenic variant in TTR (0.003%), suggesting this is a benign polymorphism found primarily in population(s) of East Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. One reputable clinical lab has classified the variant as "benign". Due to the synonymous nature of the variant along with the high allele frequency in the general population, this variant has been classified as Benign.