ClinVar Miner

Submissions for variant NM_000158.4(GBE1):c.555+1G>T (rs759707498)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000779419 SCV000916034 uncertain significance GBE1-Related Disorders 2018-11-16 criteria provided, single submitter clinical testing The GBE1 c.555+1G>T variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The c.555+1G>T variant is reported at a frequency of 0.000790 in the Latino population of the Exome Aggregation Consortium. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for GBE1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001377777 SCV001575200 likely pathogenic Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic 2020-08-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the GBE1 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 (rs759707498, ExAC 0.08%). This variant has not been reported in the literature in individuals with GBE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 632422). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GBE1 are known to be pathogenic (PMID: 15452297, 20058079). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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