rs11564447

Positions:

• chr3-41226863-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001904.4(CTNNB1):​c.937-345T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,266 control chromosomes in the GnomAD database, including 89 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 0.027 (89 hom., cov: 32)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0274 (4178/152266) while in subpopulation NFE AF= 0.0413 (2812/68024). AF 95% confidence interval is 0.0401. There are 89 homozygotes in gnomad4. There are 1954 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNB1	NM_001904.4	c.937-345T>G		intron_variant		ENST00000349496.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNB1	ENST00000349496.11	c.937-345T>G		intron_variant		1	NM_001904.4	P4

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4178 AN: 152148 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0274 AC: 4178 AN: 152266 Hom.: 89 Cov.: 32 AF XY: 0.0262 AC XY: 1954 AN XY: 74446

Gnomad4 AFR AF: 0.00693

Gnomad4 AMR AF: 0.0309

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0404 Hom.: 169

Bravo AF: 0.0282

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.2
DANN	Benign	0.88

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: rs11564447; hg19: chr3-41268354;