rs780528611
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001083962.2(TCF4):āc.330A>Cā(p.Ser110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,678 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 32)
Exomes š: 0.000020 ( 0 hom. )
Consequence
TCF4
NM_001083962.2 synonymous
NM_001083962.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.509
Genes affected
TCF4 (HGNC:11634): (transcription factor 4) This gene encodes transcription factor 4, a basic helix-loop-helix transcription factor. The encoded protein recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif first identified in immunoglobulin enhancers. This gene is broadly expressed, and may play an important role in nervous system development. Defects in this gene are a cause of Pitt-Hopkins syndrome. In addition, an intronic CTG repeat normally numbering 10-37 repeat units can expand to >50 repeat units and cause Fuchs endothelial corneal dystrophy. Multiple alternatively spliced transcript variants that encode different proteins have been described. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 18-55403493-T-G is Benign according to our data. Variant chr18-55403493-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 436962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.509 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000145 (22/152102) while in subpopulation AFR AF= 0.000507 (21/41420). AF 95% confidence interval is 0.000339. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF4 | NM_001083962.2 | c.330A>C | p.Ser110= | synonymous_variant | 6/20 | ENST00000354452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF4 | ENST00000354452.8 | c.330A>C | p.Ser110= | synonymous_variant | 6/20 | 5 | NM_001083962.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251184Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135742
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461576Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727090
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GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74290
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 24, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2016 | 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. - |
Pitt-Hopkins syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
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