ClinVar

Description

Variant summary: The FBN1 c.2855-139dupT variant involves the alteration of an intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large, broad control population, gnomAD that includes ExAC data and additional whole exome and genome sequences with an allele frequency of 29/30704 (1 homozygote) control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.001479 (22/14872 including 1 homozygote). This frequency is about 13 times the estimated maximal expected allele frequency of a pathogenic FBN1 variant (0.0001125), suggesting this is likely a benign polymorphism found primarily in population(s) of European (Non-Finnish) origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.