ClinVar

Description

Variant summary: HBB c.93-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a 3' acceptor site. Three predict the variant weakens a 3' acceptor site. The variant was absent in 251326 control chromosomes. c.93-1G>A has been reported in the literature in multiple individuals affected with Beta Thalassemia (Tadmouri_2000, Deidda_1990, Edison_2008, Bilgen_2011). The following publications have been ascertained in the context of this evaluation (PMID: 2283297, 18294253, 21333566, 10706767). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.