rs11564450

Variant names:

• chr3-41232581-C-G
• rs11564450
• NM_001904.4:c.1082-760C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001904.4(CTNNB1):​c.1082-760C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 150,812 control chromosomes in the GnomAD database, including 12,089 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 (12089 hom., cov: 30)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• 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: 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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• 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
CTNNB1	NM_001904.4	c.1082-760C>G		intron_variant	Intron 7 of 14	ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.1082-760C>G		intron_variant	Intron 7 of 14	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.1082-760C>G		intron_variant	Intron 7 of 15			ENSP00000494845.1
CTNNB1	ENST00000715152.1	n.1082-760C>G		intron_variant	Intron 7 of 15			ENSP00000520353.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59304 AN: 150694 Hom.: 12084 Cov.: 30

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.393 AC: 59340 AN: 150812 Hom.: 12089 Cov.: 30 AF XY: 0.390 AC XY: 28662 AN XY: 73538

African (AFR) AF: 0.309 AC: 12691 AN: 41122

American (AMR) AF: 0.360 AC: 5436 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1318 AN: 3458

East Asian (EAS) AF: 0.265 AC: 1359 AN: 5134

South Asian (SAS) AF: 0.399 AC: 1888 AN: 4734

European-Finnish (FIN) AF: 0.453 AC: 4717 AN: 10402

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

European-Non Finnish (NFE) AF: 0.453 AC: 30629 AN: 67592

Other (OTH) AF: 0.386 AC: 804 AN: 2084

Alfa AF: 0.411 Hom.: 1488

Bravo AF: 0.386

Asia WGS AF: 0.375 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	11
DANN	Benign	0.45
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -1

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

Other links and lift over

dbSNP: rs11564450; hg19: chr3-41274072;