3-41243045-C-A

Variant names:

• chr3-41243045-C-A
• rs9883073
• ENST00000471014.2:n.*12+3691C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471014.2(CTNNB1):​n.*12+3691C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,936 control chromosomes in the GnomAD database, including 11,813 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 0.39 (11813 hom., cov: 32)
• Consequence: CTNNB1 ENST00000471014.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 14 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471014.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNB1	ENST00000471014.2	TSL:3	n.*12+3691C>A		intron	N/A	ENSP00000495552.1	A0A2R8YG06

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58521 AN: 151818 Hom.: 11811 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.385 AC: 58539 AN: 151936 Hom.: 11813 Cov.: 32 AF XY: 0.382 AC XY: 28391 AN XY: 74262

African (AFR) AF: 0.279 AC: 11531 AN: 41394

American (AMR) AF: 0.356 AC: 5438 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1321 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1284 AN: 5160

South Asian (SAS) AF: 0.404 AC: 1944 AN: 4814

European-Finnish (FIN) AF: 0.460 AC: 4856 AN: 10556

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30868 AN: 67966

Other (OTH) AF: 0.378 AC: 796 AN: 2108

Alfa AF: 0.430 Hom.: 61255

Bravo AF: 0.373

Asia WGS AF: 0.358 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs9883073; hg19: chr3-41284536;