rs11564475

Positions:

• chr3-41238542-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001904.4(CTNNB1):​c.2137+466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 193,176 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (288 hom., cov: 32)
  • Exomes 𝑓: 0.012 (22 hom.)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.602

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-41238542-A-G is Benign according to our data. Variant chr3-41238542-A-G is described in ClinVar as [Benign]. Clinvar id is 1268785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.2137+466A>G		intron_variant		ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.2137+466A>G		intron_variant		1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.2137+466A>G		intron_variant				ENSP00000494845.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5482 AN: 152150 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0119 AC: 486 AN: 40906 Hom.: 22 AF XY: 0.0119 AC XY: 246 AN XY: 20754

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.00118

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.00280

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0361 AC: 5494 AN: 152270 Hom.: 288 Cov.: 32 AF XY: 0.0358 AC XY: 2666 AN XY: 74462

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00936 Hom.: 32

Bravo AF: 0.0410

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs11564475; hg19: chr3-41280033;