17-31226466-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_001042492.3(NF1):c.2033C>T(p.Pro678Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000142 in 1,613,768 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P678P) has been classified as Benign.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000565 AC: 86AN: 152122Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000259 AC: 65AN: 250640Hom.: 1 AF XY: 0.000244 AC XY: 33AN XY: 135458
GnomAD4 exome AF: 0.0000985 AC: 144AN: 1461528Hom.: 1 Cov.: 34 AF XY: 0.000111 AC XY: 81AN XY: 727078
GnomAD4 genome AF: 0.000558 AC: 85AN: 152240Hom.: 0 Cov.: 31 AF XY: 0.000551 AC XY: 41AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
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NF1: BS1, BS2 -
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This variant is associated with the following publications: (PMID: 24728327, 22703879, 27322474) -
not specified Benign:3Other:1
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Hereditary cancer-predisposing syndrome Uncertain:1Benign:2
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In silico models in agreement (benign);Other data supporting benign classification -
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Neurofibromatosis, type 1 Benign:1
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NF1-related disorder Benign:1
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). -
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. -
Hereditary cancer Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at