chr3-41239137-C-CTAGCTATCGTTCTTTT

Position:

• chr3-41239137-C-CTAGCTATCGTTCTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_001904.4(CTNNB1):​c.2142_2157dupTAGCTATCGTTCTTTT​(p.His720fs) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNB1 NM_001904.4 frameshift, stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 0.889

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0801 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-41239137-C-CTAGCTATCGTTCTTTT is Pathogenic according to our data. Variant chr3-41239137-C-CTAGCTATCGTTCTTTT is described in ClinVar as [Pathogenic]. Clinvar id is 225172.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.2142_2157dupTAGCTATCGTTCTTTT	p.His720fs	frameshift_variant, stop_gained	15/15	ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.2142_2157dupTAGCTATCGTTCTTTT	p.His720fs	frameshift_variant, stop_gained	15/15	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.2142_2157dupTAGCTATCGTTCTTTT	p.His720fs	frameshift_variant, stop_gained	15/16			ENSP00000494845.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Exudative vitreoretinopathy 1 Pathogenic:1

Pathogenic, no assertion criteria provided

research

Leeds Vision Research Group, University of Leeds

Apr 01, 2016

- -

Exudative vitreoretinopathy 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057519380; hg19: chr3-41280628;