ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.3882+5G>A

dbSNP: rs1553764454
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520022 SCV000620138 likely pathogenic not provided 2017-08-18 criteria provided, single submitter clinical testing The c.3882+5G>A variant in the COL4A3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. However, a different splice variant at the same position, c.3882+5G>C, has been reported in the heterozygous state with another COL4A3 variant in an individual with Alport syndrome (Zhang et al., 2012). The c.3882+5G>A splice site variant is predicted to destroy the natural splice donor site in intron 43, and is expected to cause abnormal gene splicing. The c.3882+5G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.3882+5G>A as a likely pathogenic variant.
Athena Diagnostics RCV000520022 SCV004229444 pathogenic not provided 2022-12-14 criteria provided, single submitter clinical testing This variant appears to be associated with Alport syndrome in at least one family, however, the available information does not rule out an apparent association due to chance. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal RNA splicing (PMID: 29098738).
Labcorp Genetics (formerly Invitae), Labcorp RCV000520022 SCV004540387 pathogenic not provided 2023-08-07 criteria provided, single submitter clinical testing Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 29098738). ClinVar contains an entry for this variant (Variation ID: 451439). This variant has been observed in individuals with Alport syndrome (PMID: 24033287, 29098738). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 43 of the COL4A3 gene. It does not directly change the encoded amino acid sequence of the COL4A3 protein. It affects a nucleotide within the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Medical Genetics, University of Parma RCV001089908 SCV001245141 uncertain significance Autosomal recessive Alport syndrome 2020-03-11 flagged submission clinical testing

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