ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4816+4A>G

dbSNP: rs2141269898
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001920083 SCV002162237 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-03-11 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This sequence change falls in intron 39 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 not present in population databases (gnomAD no frequency). 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 may disrupt the consensus splice site. 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.
All of Us Research Program, National Institutes of Health RCV004010804 SCV004825521 uncertain significance Marfan syndrome 2023-05-16 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +4 position of intron 39 of the FBN1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV004728913 SCV005336777 uncertain significance FBN1-related disorder 2024-09-06 no assertion criteria provided clinical testing The FBN1 c.4816+4A>G variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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