rs756653022
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6BP7BS2_Supporting
The NM_001042492.3(NF1):c.3732T>A(p.Val1244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001042492.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.3732T>A | p.Val1244= | synonymous_variant | 28/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.3732T>A | p.Val1244= | synonymous_variant | 28/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.3732T>A | p.Val1244= | synonymous_variant | 28/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251402Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135878
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461820Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727214
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 08, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 17, 2014 | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 05, 2016 | p.Val1244Val variant in NF1 has been identified in 4/66738 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/, dbSN P rs756653022). While the variant does not alter an amino acid residue, computat ional tools suggest the creation of a novel splice site. However, this informati on is not predictive enough to determine pathogenicity. Although a role in disea se cannot be fully excluded, its presence in the general population and lack of impact to the protein sequence suggests that it is likely to be benign. - |
NF1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 10, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Neurofibromatosis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at