rs748653573

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001904.4(CTNNB1):c.2128C>A(p.Arg710Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R710H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CTNNB1
NM_001904.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.64

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

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

CTNNB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19088176).

BS2

High AC in GnomAdExome4 at 9 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNB1	NM_001904.4 link	c.2128C>A	p.Arg710Ser	missense_variant	Exon 14 of 15	ENST00000349496.11	NP_001895.1	P35222A0A024R2Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTNNB1	ENST00000349496.11 link	c.2128C>A	p.Arg710Ser	missense_variant	Exon 14 of 15	1	NM_001904.4	ENSP00000344456.5	P35222
CTNNB1	ENST00000645982.1 link	c.2128C>A	p.Arg710Ser	missense_variant	Exon 14 of 16			ENSP00000494845.1	P35222
CTNNB1	ENST00000715152.1 link	n.*44C>A		non_coding_transcript_exon_variant	Exon 14 of 16			ENSP00000520353.1
CTNNB1	ENST00000715152.1 link	n.*44C>A		3_prime_UTR_variant	Exon 14 of 16			ENSP00000520353.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251354

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461138

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1111342

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.31

T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;.;T;T;T;T;.;.;T;T;.;T;T;T;T;.;T;T;T;T;T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.033

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;D;.;.;.;.;D;D;.;.;D;.;.;.;.;D;.;D;.;.;.;.;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

N;N;.;N;N;N;N;N;.;N;N;.;.;N;N;N;.;.;.;.;N;N;.;.;N;.;.;N;N;.;N;.;N;.;N;N;N;N;N

PhyloP100

4.6

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.47

.;.;.;N;.;.;.;.;.;N;N;.;.;N;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.17

Sift

Benign

0.76

.;.;.;T;.;.;.;.;.;T;T;.;.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.76

.;.;.;T;.;.;.;.;.;T;T;.;.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Polyphen

0.0020

B;B;.;B;B;B;B;B;.;B;B;.;.;B;B;B;.;.;.;.;B;B;.;.;B;.;.;B;B;.;B;.;B;.;B;B;B;B;B

Vest4

0.91, 0.92, 0.91, 0.90, 0.91

MutPred

0.38

Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;.;.;.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;.;Loss of catalytic residue at R710 (P = 0.0082);.;.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);.;Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);Loss of catalytic residue at R710 (P = 0.0082);

MVP

0.88

MPC

0.25

ClinPred

0.43

GERP RS

5.2

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.37

gMVP

0.51

Mutation Taster

=1/99

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over