Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001290588 | SCV001478672 | uncertain significance | not specified | 2021-01-07 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.*47C>G is located in the untranslated mRNA region downstream of the termination codon. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a 5' prime donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251122 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.*47C>G has been reported in the literature in at least one individual affected with a mild beta-thalassaemia intermedia phenotype, who also carried a beta(0) HBB variant in trans (Ho_1998). These data do not allow clear conclusions about variant significance. At least one publication reported experimental evidence evaluating an impact on protein expression, and demonstrated that the variant results in a decreased expression efficiency, corresponding to about 70-80% of the expression of the wild type 3' UTR sequence (Hino_2012). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. In addition, another variant affecting the same nucleotide (c.*47C>T) has been classified as VUS by our laboratory. Based on the evidence outlined above, the variant was classified as uncertain significance. |