rs11564452

Variant names:

• chr3-41232779-A-T
• rs11564452
• NM_001904.4:c.1082-562A>T

Variant summary

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

The NM_001904.4(CTNNB1):​c.1082-562A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,752 control chromosomes in the GnomAD database, including 12,242 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 (12242 hom., cov: 31)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001904.4. 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
	CTNNB1	NM_001904.4	MANE Select	c.1082-562A>T		intron	N/A	NP_001895.1	P35222
	CTNNB1	NM_001098209.2		c.1082-562A>T		intron	N/A	NP_001091679.1	P35222
	CTNNB1	NM_001098210.2		c.1082-562A>T		intron	N/A	NP_001091680.1	P35222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNB1	ENST00000349496.11	TSL:1 MANE Select	c.1082-562A>T		intron	N/A	ENSP00000344456.5	P35222
	CTNNB1	ENST00000396183.7	TSL:1	c.1082-562A>T		intron	N/A	ENSP00000379486.3	P35222
	CTNNB1	ENST00000396185.8	TSL:1	c.1082-562A>T		intron	N/A	ENSP00000379488.3	P35222

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59877 AN: 151634 Hom.: 12238 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.395 AC: 59905 AN: 151752 Hom.: 12242 Cov.: 31 AF XY: 0.392 AC XY: 29047 AN XY: 74180

African (AFR) AF: 0.306 AC: 12665 AN: 41374

American (AMR) AF: 0.364 AC: 5544 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3464

East Asian (EAS) AF: 0.266 AC: 1371 AN: 5154

South Asian (SAS) AF: 0.405 AC: 1937 AN: 4788

European-Finnish (FIN) AF: 0.458 AC: 4819 AN: 10516

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30938 AN: 67906

Other (OTH) AF: 0.387 AC: 814 AN: 2106

Alfa AF: 0.415 Hom.: 1689

Bravo AF: 0.385

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.79
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11564452; hg19: chr3-41274270;