3-41200847-C-A

Variant names:

• chr3-41200847-C-A
• rs4533622
• NM_001904.4:c.-49+1177C>A

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+1177C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,102 control chromosomes in the GnomAD database, including 12,440 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 (12440 hom., cov: 32)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 17 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: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, Ambry Genetics
• exudative vitreoretinopathy 7

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• 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 rank	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.-49+1177C>A		intron_variant	Intron 1 of 14	ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.-49+1177C>A		intron_variant	Intron 1 of 14	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.-49+1177C>A		intron_variant	Intron 1 of 15			ENSP00000494845.1
CTNNB1	ENST00000715152.1	n.-49+1177C>A		intron_variant	Intron 1 of 15			ENSP00000520353.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60526 AN: 151984 Hom.: 12438 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.398 AC: 60555 AN: 152102 Hom.: 12440 Cov.: 32 AF XY: 0.394 AC XY: 29331 AN XY: 74356

African (AFR) AF: 0.320 AC: 13296 AN: 41490

American (AMR) AF: 0.366 AC: 5587 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1324 AN: 3472

East Asian (EAS) AF: 0.249 AC: 1286 AN: 5174

South Asian (SAS) AF: 0.398 AC: 1919 AN: 4822

European-Finnish (FIN) AF: 0.459 AC: 4857 AN: 10574

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

European-Non Finnish (NFE) AF: 0.455 AC: 30951 AN: 67976

Other (OTH) AF: 0.393 AC: 829 AN: 2112

Alfa AF: 0.360 Hom.: 2641

Bravo AF: 0.389

Asia WGS AF: 0.361 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.78
DANN	Benign	0.70
PhyloP100		-1.0
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)		0.0		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: rs4533622; hg19: chr3-41242338;