rs3915129

Positions:

• chr3-41202251-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001904.4(CTNNB1):​c.-49+2581T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,016 control chromosomes in the GnomAD database, including 12,642 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 0.40 (12642 hom., cov: 32)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNB1	NM_001904.4	c.-49+2581T>G		intron_variant		ENST00000349496.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNB1	ENST00000349496.11	c.-49+2581T>G		intron_variant		1	NM_001904.4	P4

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61120 AN: 151898 Hom.: 12636 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.402 AC: 61155 AN: 152016 Hom.: 12642 Cov.: 32 AF XY: 0.398 AC XY: 29609 AN XY: 74314

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.395

Alfa AF: 0.436 Hom.: 14889

Bravo AF: 0.393

Asia WGS AF: 0.367 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3915129; hg19: chr3-41243742;