ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.11077-1G>A

dbSNP: rs1458096844
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000794175 SCV000933566 likely pathogenic Nemaline myopathy 2 2024-03-25 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 74 of the NEB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 641029). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV000794175 SCV005849539 likely pathogenic Nemaline myopathy 2 2023-06-22 criteria provided, single submitter clinical testing The invariant splice acceptor c.11077-1G>A variant in NEB gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.11077-1G>A variant is absent in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic. SplieAI predicts this variant to cause splice acceptor loss (1.00) and acceptor gain (0.98). Loss of function variants have been previously reported to be disease causing (Lehtokari VL, et al., 2014). However, additional functional studies will be required to prove the pathogenicity of this variant conclusively. For these reasons, this variant has been classified as Likely Pathogenic.

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