rs11564450

Positions:

• chr3-41232581-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.1082-760C>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.1082-760C>G		intron_variant		1	NM_001904.4	ENSP00000344456	P4

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

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.386

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11564450; hg19: chr3-41274072;