ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4332+1G>A

dbSNP: rs1555618572
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000582123 SCV000753635 pathogenic Neurofibromatosis, type 1 2023-07-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 31 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). Disruption of this splice site has been observed in individuals with neurofibromatosis type I (PMID: 16461335, 17311297, 28961165). ClinVar contains an entry for this variant (Variation ID: 492881). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000582123 SCV001479034 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000582123 SCV002560039 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002330999 SCV002627794 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-09-25 criteria provided, single submitter clinical testing The c.4269+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 31 of the NF1 gene. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Baylor Genetics RCV003465317 SCV004190781 pathogenic Juvenile myelomonocytic leukemia 2022-11-03 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000582123 SCV000692353 pathogenic Neurofibromatosis, type 1 2017-08-08 no assertion criteria provided clinical testing

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