ClinVar

Description

Variant summary: HBB c.*110_*111delTA is located in the untranslated mRNA region downstream of the termination codon that lies in the 'known' polyA tail signal (AATAAA) of HBB, and mutations in this region are known to reduce the synthesis of mRNA. Therefore, this variant is expected or likely to interfere with cleavage of transcript and addition of polyA tail, leading to an elongated transcript that is unstable (Orkin 1985). The variant allele was found at a frequency of 5.9e-06 in 1015192 control chromosomes (gnomAD database v4). c.*110_*111delTA has been reported twice in literature, one individual diagnosed with BTHAL and one individual having typical features of BTHAL minor (Ghanem_1992, Kimberland_1995). Ithanet lists variant as a "Globin gene causative mutation". In the same region, a variant c.*110T>C and c.*111A>G have been reported in literature as a common pathogenic variants. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 1301930, 21423179, 7599641). ClinVar contains an entry for this variant (Variation ID: 632843). Based on the evidence outlined above, the variant was classified as likely pathogenic.