Variant 3-41237949-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001904.4(CTNNB1):c.2077-67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,341,932 control chromosomes in the GnomAD database, including 41,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3718 hom., cov: 32)

Exomes 𝑓: 0.24 ( 37351 hom. )

Consequence

CTNNB1
NM_001904.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.93

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:

CTNNB1 (HGNC:):

CTNNB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-41237949-A-G is Benign according to our data. Variant chr3-41237949-A-G is described in ClinVar as [Benign]. Clinvar id is 1276603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNB1	NM_001904.4 linkuse as main transcript	c.2077-67A>G		intron_variant		ENST00000349496.11	NP_001895.1	P35222A0A024R2Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11 linkuse as main transcript	c.2077-67A>G		intron_variant		1	NM_001904.4	ENSP00000344456.5		P35222
CTNNB1	ENST00000645982.1 linkuse as main transcript	c.2077-67A>G		intron_variant				ENSP00000494845.1		P35222

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29226

AN:

151962

Hom.:

3703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.240

AC:

284973

AN:

1189852

Hom.:

37351

Cov.:

AF XY:

0.239

AC XY:

144789

AN XY:

605686

show subpopulations

Gnomad4 AFR exome

AF:

0.0385

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.530

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.192

AC:

29246

AN:

152080

Hom.:

3718

Cov.:

AF XY:

0.193

AC XY:

14329

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.536

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.230

Hom.:

6136

Bravo

AF:

0.194

Asia WGS

AF:

0.306

AC:

1063

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.79

CADD

Benign

1.6

DANN

Benign

0.84

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