rs370160994
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BS2_SupportingBA1
This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Val168= variant in TCF4 is 0.057% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Val168= variant is observed in 1 unaffected individual (Baylor Genetics internal database) (BS2_supporting). In summary, p.Val168= variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BA1, BS2_supporting). LINK:https://erepo.genome.network/evrepo/ui/classification/CA293878/MONDO:0012589/016
Frequency
Consequence
NM_001083962.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000319 AC: 80AN: 250828Hom.: 0 AF XY: 0.000339 AC XY: 46AN XY: 135544
GnomAD4 exome AF: 0.000491 AC: 718AN: 1461288Hom.: 1 Cov.: 31 AF XY: 0.000498 AC XY: 362AN XY: 726948
GnomAD4 genome AF: 0.000348 AC: 53AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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TCF4: BP4, BP7 -
not specified Benign:2
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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. -
Pitt-Hopkins syndrome Benign:2
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The allele frequency of the p.Val168= variant in TCF4 is 0.057% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Val168= variant is observed in 1 unaffected individual (Baylor Genetics internal database) (BS2_supporting). In summary, p.Val168= variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BA1, BS2_supporting). -
Inborn genetic diseases 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. -
TCF4-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). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at