rs17883614
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001042492.3(NF1):c.6642+45T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 1,555,824 control chromosomes in the GnomAD database, including 5,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.12 ( 3032 hom., cov: 32)
Exomes 𝑓: 0.024 ( 2942 hom. )
Consequence
NF1
NM_001042492.3 intron
NM_001042492.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.98
Genes affected
NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
?
Variant 17-31337627-T-A is Benign according to our data. Variant chr17-31337627-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 257297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.6642+45T>A | intron_variant | ENST00000358273.9 | |||
NF1 | NM_000267.3 | c.6579+45T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.6642+45T>A | intron_variant | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.121 AC: 18332AN: 152076Hom.: 3025 Cov.: 32
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GnomAD3 exomes AF: 0.0470 AC: 10963AN: 233198Hom.: 1178 AF XY: 0.0428 AC XY: 5449AN XY: 127256
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GnomAD4 exome AF: 0.0243 AC: 34071AN: 1403630Hom.: 2942 Cov.: 25 AF XY: 0.0242 AC XY: 16944AN XY: 700742
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GnomAD4 genome ? AF: 0.121 AC: 18355AN: 152194Hom.: 3032 Cov.: 32 AF XY: 0.119 AC XY: 8866AN XY: 74416
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Neurofibromatosis, type 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 13, 2022 | - - |
Neurofibromatosis, familial spinal Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at