ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3708+3_3708+6del

dbSNP: rs2151435840
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001924833 SCV002155433 uncertain significance Neurofibromatosis, type 1 2021-05-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 27 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site of the intron.
CeGaT Center for Human Genetics Tuebingen RCV004809689 SCV005435591 uncertain significance not provided 2024-09-01 criteria provided, single submitter clinical testing NF1: PM2, PP3, PP4
PreventionGenetics, part of Exact Sciences RCV004552077 SCV004723256 uncertain significance NF1-related disorder 2023-10-23 no assertion criteria provided clinical testing The NF1 c.3708+3_3708+6delAAGT variant is predicted to result in an intronic deletion. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. However, other intronic variants predicted to affect splicing at the same donor site have been reported in patients with features consistent with neurofibromatosis type 1 (c.3708+3A>T, c.3708+5G>A, Assunto et al. 2019. PubMed ID: 31730495, Koster et al. 2021. PubMed ID: 34782607). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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