3-41225198-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_001904.4(CTNNB1):c.486C>T(p.Asp162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 2 hom. )
Consequence
CTNNB1
NM_001904.4 synonymous
NM_001904.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.242
Genes affected
CTNNB1 (HGNC:2514): (catenin beta 1) The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 3-41225198-C-T is Benign according to our data. Variant chr3-41225198-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210806.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1, Likely_benign=1}.
BP7
Synonymous conserved (PhyloP=-0.242 with no splicing effect.
BS2
High AC in GnomAd4 at 184 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNB1 | NM_001904.4 | c.486C>T | p.Asp162= | synonymous_variant | 4/15 | ENST00000349496.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNB1 | ENST00000349496.11 | c.486C>T | p.Asp162= | synonymous_variant | 4/15 | 1 | NM_001904.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00121 AC: 184AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00125 AC: 315AN: 251220Hom.: 1 AF XY: 0.00130 AC XY: 176AN XY: 135766
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GnomAD4 exome AF: 0.00123 AC: 1797AN: 1461744Hom.: 2 Cov.: 32 AF XY: 0.00126 AC XY: 916AN XY: 727166
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GnomAD4 genome AF: 0.00121 AC: 184AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97AN XY: 74478
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | CTNNB1: BP4, BP7, BS1 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 26, 2014 | - - |
CTNNB1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 10, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at