ClinVar

Description

Variant summary: HBB c.316-99delT is located at a position not widely known to affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. Though deep intronic positions are not widely known to affect splicing, this intronic region does harbor pathogenic HBB variants such as c.316-106C>G, c.316-146T>G and c.316-197C>T (all are classified as pathogenic in our internal database). The frequency of this variant in the general population could not be determined as the technology used for large population databases (ExAC, gnomAD, ESP, 1000G) cannot detect variants of this type. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.316-99delT in individuals affected with Hemoglobinopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.