rs3915129

Variant names:

• chr3-41202251-T-G
• rs3915129
• NM_001904.4:c.-49+2581T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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 Gene-Disease associations (from GenCC):

• exudative vitreoretinopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• severe intellectual disability-progressive spastic diplegia syndrome

  Inheritance: Unknown, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• exudative vitreoretinopathy 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001904.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNB1	NM_001904.4	MANE Select	c.-49+2581T>G		intron	N/A	NP_001895.1	P35222
	CTNNB1	NM_001098209.2		c.-49+2581T>G		intron	N/A	NP_001091679.1	P35222
	CTNNB1	NM_001098210.2		c.-49+2581T>G		intron	N/A	NP_001091680.1	P35222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNB1	ENST00000349496.11	TSL:1 MANE Select	c.-49+2581T>G		intron	N/A	ENSP00000344456.5	P35222
	CTNNB1	ENST00000396183.7	TSL:1	c.-49+2581T>G		intron	N/A	ENSP00000379486.3	P35222
	CTNNB1	ENST00000396185.8	TSL:1	c.-49+2581T>G		intron	N/A	ENSP00000379488.3	P35222

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

African (AFR) AF: 0.334 AC: 13839 AN: 41470

American (AMR) AF: 0.367 AC: 5601 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1322 AN: 3462

East Asian (EAS) AF: 0.247 AC: 1280 AN: 5174

South Asian (SAS) AF: 0.407 AC: 1961 AN: 4814

European-Finnish (FIN) AF: 0.459 AC: 4846 AN: 10550

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30969 AN: 67952

Other (OTH) AF: 0.395 AC: 834 AN: 2112

Alfa AF: 0.432 Hom.: 18970

Bravo AF: 0.393

Asia WGS AF: 0.367 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.66
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3915129; hg19: chr3-41243742;