ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.828+1G>A (rs763290176)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673023 SCV000798187 pathogenic Classic homocystinuria 2018-02-27 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000673023 SCV000898571 likely pathogenic Classic homocystinuria 2018-02-13 criteria provided, single submitter clinical testing CBS NM_000071.2 exon 9 c.828+1G>A: This variant has been reported in the literature as a compound heterozygote in 1 individual with homocystinuria (Kraus 1999 PMID:10338090). This variant is present in 2/110146 European alleles in the Genome Aggregation Database ( Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population and/or variable expressivity. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function variants have been reported in association with disease for this gene (Kraus 1999 PMID:10338090). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.
Invitae RCV000673023 SCV000961094 pathogenic Classic homocystinuria 2020-01-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the CBS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs763290176, ExAC 0.002%). This variant has been observed in individuals affected with homocystinuria (PMID: 15365998, 29352562). This variant is also known as IVS7+1G>A, 8297G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 556952). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196718 SCV001367349 pathogenic Cryptorchidism; Expressive language delay; Seizures; Abnormality of the dentition; Overfolded helix; Frontal upsweep of hair; Microdontia of primary teeth; Infantile spasms 2019-08-29 criteria provided, single submitter clinical testing This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BS2,BP4. This variant was detected in hemizygous state.

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