rs2953

chr3-41239897-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001904.4(CTNNB1):c.*555T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.422 in 211,094 control chromosomes in the GnomAD database, including 18,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (12658 hom., cov: 28)
  • Exomes 𝑓: 0.45 (6167 hom.)
• Consequence: CTNNB1 NM_001904.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.19

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=-0.43).
• BP6: Variant 3-41239897-T-G is Benign according to our data. Variant chr3-41239897-T-G is described in ClinVar as [Benign]. Clinvar id is 1235713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNB1	NM_001904.4	c.*555T>G		3_prime_UTR_variant	15/15	ENST00000349496.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNB1	ENST00000349496.11	c.*555T>G		3_prime_UTR_variant	15/15	1	NM_001904.4	P4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 60907 AN: 148524 Hom.: 12657 Cov.: 28

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.450 AC: 28143 AN: 62484 Hom.: 6167 Cov.: 0 AF XY: 0.451 AC XY: 13087 AN XY: 29012

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.410 AC: 60924 AN: 148610 Hom.: 12658 Cov.: 28 AF XY: 0.406 AC XY: 29354 AN XY: 72260

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.403

Alfa AF: 0.445 Hom.: 12732

Bravo AF: 0.399

Asia WGS AF: 0.376 AC: 1311 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 33789307, 30280518) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	15
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2953; hg19: chr3-41281388;