Variant 3-41239316-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001904.4(CTNNB1):c.2320C>T(p.Leu774=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,614,094 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 21 hom. )

Consequence

CTNNB1
NM_001904.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.51

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-41239316-C-T is Benign according to our data. Variant chr3-41239316-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-41239316-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.51 with no splicing effect.

BS2

High AC in GnomAd4 at 570 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNB1	NM_001904.4 linkuse as main transcript	c.2320C>T	p.Leu774=	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.2320C>T	p.Leu774=	synonymous_variant	15/15	1	NM_001904.4	P4

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

570

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00382

AC:

958

AN:

250610

Hom.:

AF XY:

0.00376

AC XY:

510

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00731

Gnomad NFE exome

AF:

0.00571

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00528

AC:

7713

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

3664

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00863

Gnomad4 NFE exome

AF:

0.00608

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.00374

AC:

570

AN:

152330

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00438

Hom.:

Bravo

AF:

0.00339

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00534

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CTNNB1: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 10, 2015

- -

Medulloblastoma;C0206711:Pilomatrixoma;C0346629:Colorectal cancer;C0919267:Ovarian neoplasm;C2239176:Hepatocellular carcinoma;C3554449:Severe intellectual disability-progressive spastic diplegia syndrome;C4539767:Exudative vitreoretinopathy 7

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.0

DANN

Benign

0.73

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