Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV001281059 | SCV001468484 | uncertain significance | Atypical hemolytic-uremic syndrome with B factor anomaly; Age related macular degeneration 14; Complement factor b deficiency | 2021-03-30 | criteria provided, single submitter | clinical testing | CFB NM_001710.5 exon 4 c.658+7T>C: This variant has not been reported in the literature but is present in 0.1% (40/23766) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/6-31915305-T-C?dataset=gnomad_r2_1). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Although this variant occurs in the splice region, computational prediction tools do not suggest that it alters splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Labcorp Genetics |
RCV002069496 | SCV002403105 | benign | not provided | 2023-10-25 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004699266 | SCV005203098 | uncertain significance | not specified | 2024-07-09 | criteria provided, single submitter | clinical testing | Variant summary: CFB c.658+7T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation 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 0.00012 in 246164 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CFB causing Age-related Macular Degeneration, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.658+7T>C in individuals affected with Age-related Macular Degeneration and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 992561). Based on the evidence outlined above, the variant was classified as uncertain significance. |