rs2293303

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001904.4(CTNNB1):c.2340C>T(p.Asp780=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00879 in 1,613,700 control chromosomes in the GnomAD database, including 933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 823 hom. )

Consequence

CTNNB1
NM_001904.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.77

Variant links:

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]

CTNNB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 3-41239336-C-T is Benign according to our data. Variant chr3-41239336-C-T is described in ClinVar as [Benign]. Clinvar id is 128869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNB1	NM_001904.4 linkuse as main transcript	c.2340C>T	p.Asp780=	synonymous_variant	15/15	ENST00000349496.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNB1	ENST00000349496.11 linkuse as main transcript	c.2340C>T	p.Asp780=	synonymous_variant	15/15	1	NM_001904.4	P4

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2143

AN:

152206

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0815

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0317

AC:

7910

AN:

249468

Hom.:

592

AF XY:

0.0255

AC XY:

3443

AN XY:

135044

show subpopulations

Gnomad AFR exome

AF:

0.00345

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.00298

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.00824

AC:

12044

AN:

1461376

Hom.:

823

Cov.:

AF XY:

0.00743

AC XY:

5403

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.00342

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000241

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0141

AC:

2146

AN:

152324

Hom.:

110

Cov.:

AF XY:

0.0155

AC XY:

1158

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00356

Gnomad4 AMR

AF:

0.0817

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.00662

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.0590

AC:

207

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over