ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1468+4C>T

gnomAD frequency: 0.00002  dbSNP: rs765579667
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000600067 SCV000727890 likely benign not specified 2018-02-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health RCV001181631 SCV001346814 likely benign Familial thoracic aortic aneurysm and aortic dissection 2019-09-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001860329 SCV002152645 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-10-29 criteria provided, single submitter clinical testing This sequence change falls in intron 12 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 (rs765579667, gnomAD 0.006%). This variant has been observed in individual(s) with Marfan syndrome (PMID: 31098894). ClinVar contains an entry for this variant (Variation ID: 515684). 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.
All of Us Research Program, National Institutes of Health RCV004002596 SCV004843663 likely benign Marfan syndrome 2024-02-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV001181631 SCV005032422 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-11-27 criteria provided, single submitter clinical testing The c.1468+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 11 in the FBN1 gene. This alteration has been reported in a Marfan syndrome and related diseases cohort (Li J et al. Sci China Life Sci, 2019 Dec;62:1630-1637). This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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