rs2293303

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001904.4(CTNNB1):c.2340C>T(p.Asp780Asp) 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:6

Conservation

PhyloP100: 4.77

Publications

18 publications found

Variant links:

COSMIC-nc: COSV62704170

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 Gene-Disease associations (from GenCC):

exudative vitreoretinopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
severe intellectual disability-progressive spastic diplegia syndrome
Inheritance: Unknown, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
exudative vitreoretinopathy 7
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CTNNB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001904.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTNNB1	NM_001904.4	MANE Select	c.2340C>T	p.Asp780Asp	synonymous	Exon 15 of 15	NP_001895.1	P35222
CTNNB1	NM_001098209.2		c.2340C>T	p.Asp780Asp	synonymous	Exon 15 of 16	NP_001091679.1	P35222
CTNNB1	NM_001098210.2		c.2340C>T	p.Asp780Asp	synonymous	Exon 15 of 16	NP_001091680.1	P35222

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTNNB1	ENST00000349496.11	TSL:1 MANE Select	c.2340C>T	p.Asp780Asp	synonymous	Exon 15 of 15	ENSP00000344456.5	P35222
CTNNB1	ENST00000396183.7	TSL:1	c.2340C>T	p.Asp780Asp	synonymous	Exon 15 of 16	ENSP00000379486.3	P35222
CTNNB1	ENST00000396185.8	TSL:1	c.2340C>T	p.Asp780Asp	synonymous	Exon 15 of 16	ENSP00000379488.3	P35222

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

GnomAD2 exomes

AF:

0.0317

AC:

7910

AN:

249468

AF XY:

0.0255

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 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

African (AFR)

AF:

0.00209

AC:

AN:

33472

American (AMR)

AF:

0.140

AC:

6221

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.111

AC:

4401

AN:

39666

South Asian (SAS)

AF:

0.00342

AC:

295

AN:

86208

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000241

AC:

268

AN:

1111812

Other (OTH)

AF:

0.0129

AC:

779

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

609

1217

1826

2434

3043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0141

AC:

2146

AN:

152324

Hom.:

110

Cov.:

AF XY:

0.0155

AC XY:

1158

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00356

AC:

148

AN:

41568

American (AMR)

AF:

0.0817

AC:

1251

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.125

AC:

648

AN:

5180

South Asian (SAS)

AF:

0.00662

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68034

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00811

Hom.:

120

Bravo

AF:

0.0212

Asia WGS

AF:

0.0590

AC:

207

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=85/15

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over