Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000507852 | SCV000052644 | uncertain significance | not specified | 2022-12-19 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.316-96G>C 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. The variant allele was found at a frequency of 0.00038 in 150934 control chromosomes (gnomAD v3.1.2), predominantly at a frequency of 0.00075 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in HBB causing Hemoglobinopathy (0.00038 vs 0.011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.316-96G>C in individuals affected with Hemoglobinopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed this variant since 2014: one classified the variant as uncertain significance and one as likely benign. There are several reported disease variants described within this intron (e.g. c.316-3C>A, c.316-7C>A, c.316-12T>C, c.316-14T>G, c.316-106C>G, c.316-146T>G, and c.316-197C>T) and some have been shown to generate an alternative splice-site, suggesting this deep intronic variant should be interpreted with caution. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000874728 | SCV000601285 | uncertain significance | not provided | 2023-08-21 | criteria provided, single submitter | clinical testing | The HBB c.316-96G>C variant, to the best of our knowledge, has not been reported in the published literature. The frequency of this variant in the general population, 0.00045 (7/15430 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect HBB mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. |
Invitae | RCV000874728 | SCV001016948 | likely benign | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing |