ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3870+1G>A

dbSNP: rs1131691075
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492394 SCV000581255 pathogenic Hereditary cancer-predisposing syndrome 2014-08-22 criteria provided, single submitter clinical testing The c.3870+1G>A pathogenic mutation results from a G to A substitution one nucleotide after exon 28 of the NF1 gene. A pathogenic mutation, c.3870+1G>T,<span data-redactor="verified" style="background-color: initial;">which occurs at the same position as<span data-redactor="verified" style="background-color: initial;">c.3870+1G>A,<span data-redactor="verified" style="background-color: initial;">has been seen in one individual with<span data-redactor="verified" style="background-color: initial;">cafe au lait spots, greater than fifty neurofibromas, freckling, lisch nodules, and leg plexiform neurofibromas (<span data-redactor="verified" style="background-color: initial;">Serra E et al. Nat Genet.2001;28(3):294-6).<span data-redactor="verified" style="background-color: initial;">In addition to the clinical data presented in the literature, since alterations that disrupt the canonical splice donor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp RCV001201978 SCV001373073 pathogenic Neurofibromatosis, type 1 2022-02-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 28 of the NF1 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 NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 428951). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 11115850, 11431704).
Genome-Nilou Lab RCV001201978 SCV002560002 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV001201978 SCV002581814 likely pathogenic Neurofibromatosis, type 1 2022-08-25 criteria provided, single submitter clinical testing
GeneDx RCV003235250 SCV003932898 pathogenic not provided 2022-12-15 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing leading to an in-frame deletion of the adjacent exon; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); This variant is associated with the following publications: (PMID: 25525159, 10712197, 17311297, 23913538, 11431704)

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