dbSNP rs3864004: CTNNB1:c.-144G>A (chr3-41198686-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000431914.6(CTNNB1):c.-144G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,228 control chromosomes in the GnomAD database, including 12,372 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12368 hom., cov: 34)

Exomes 𝑓: 0.43 ( 4 hom. )

Consequence

CTNNB1
ENST00000431914.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

Publications

35 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CTNNB1	ENST00000431914.6 link	c.-144G>A	5_prime_UTR_variant	Exon 1 of 16	4	ENSP00000412219.2	P35222
CTNNB1	ENST00000642992.1 link	c.-144G>A	5_prime_UTR_variant	Exon 1 of 15		ENSP00000496385.1	P35222
CTNNB1	ENST00000405570.6 link	c.-49+2980G>A	intron_variant	Intron 2 of 16	2	ENSP00000385604.1	P35222

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60332

AN:

152066

Hom.:

12366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.391

GnomAD4 exome

AF:

0.432

AC:

AN:

Hom.:

Cov.:

AF XY:

0.423

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.382

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

AF:

0.397

AC:

60361

AN:

152184

Hom.:

12368

Cov.:

AF XY:

0.393

AC XY:

29237

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.319

AC:

13244

AN:

41542

American (AMR)

AF:

0.363

AC:

5557

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1326

AN:

3470

East Asian (EAS)

AF:

0.249

AC:

1286

AN:

5160

South Asian (SAS)

AF:

0.401

AC:

1936

AN:

4822

European-Finnish (FIN)

AF:

0.460

AC:

4856

AN:

10568

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30828

AN:

67992

Other (OTH)

AF:

0.388

AC:

822

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1926

3852

5779

7705

9631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.435

Hom.:

25709

Bravo

AF:

0.387

Asia WGS

AF:

0.361

AC:

1260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.60

(source)

DANN

Benign

0.88

PhyloP100

-0.0060

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over