ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.4773+3A>G (rs759672616)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408554 SCV000281905 pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000425309 SCV000511900 pathogenic not provided 2015-09-03 criteria provided, single submitter clinical testing The c.4773+3 A>G splice site variant in the ABCA4 gene has been previously reported in association with Stargardt disease (Duno et al., 2012; Jonsson et al., 2013; Braun et al., 2013). This variant is predicted to destroy the canonical splice donor site in intron 33. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.4773+3 A>G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000425309 SCV001227047 pathogenic not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change falls in intron 33 of the ABCA4 gene. It does not directly change the encoded amino acid sequence of the ABCA4 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs759672616, ExAC 0.03%). This variant has been observed in individual(s) with clinical features of ABCA4-related conditions (PMID: 23443024, 23918662, 29555955, 30718709). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 236122). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 28118664, 29162642). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000787761 SCV001241368 pathogenic Retinal dystrophy 2019-05-21 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000425309 SCV001248239 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787761 SCV000926766 uncertain significance Retinal dystrophy 2018-04-01 no assertion criteria provided research

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