ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6616+5A>G

gnomAD frequency: 0.00002  dbSNP: rs1381778697
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177390 SCV001341588 likely benign Familial thoracic aortic aneurysm and aortic dissection 2019-01-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001875845 SCV002123549 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-12-18 criteria provided, single submitter clinical testing This sequence change falls in intron 54 of the FBN1 gene. It does not directly change the encoded amino acid sequence of the FBN1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 919291). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001177390 SCV002664475 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-09-03 criteria provided, single submitter clinical testing The c.6616+5A>G intronic variant results from an A to G substitution 5 nucleotides after coding exon 53 in the FBN1 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004538405 SCV004717963 likely benign FBN1-related disorder 2021-02-16 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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