Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001471008 | SCV001675110 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-03-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155411 | SCV003844379 | likely benign | not specified | 2023-02-06 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.1147+7G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA 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 6e-05 in 150886 control chromosomes, predominantly at a frequency of 0.00022 within the African or African-American subpopulation in the gnomAD database (v3.1 genome dataset), including 1 homozygote. The observed variant frequency within the African or African-American control individuals is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in FBN1 causing Marfan Syndrome phenotype (0.00011), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.1147+7G>A in individuals affected with Marfan Syndrome 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, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |