3-41245527-T-C

Variant names:

• chr3-41245527-T-C
• rs11711946
• ENST00000471014.2:n.*12+6173T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471014.2(CTNNB1):​n.*12+6173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,060 control chromosomes in the GnomAD database, including 10,937 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 0.36 (10937 hom., cov: 32)
• Consequence: CTNNB1 ENST00000471014.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 12 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=-0.93).
• 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000471014.2	n.*12+6173T>C		intron_variant	Intron 4 of 5	3		ENSP00000495552.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54914 AN: 151942 Hom.: 10936 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.361 AC: 54927 AN: 152060 Hom.: 10937 Cov.: 32 AF XY: 0.358 AC XY: 26622 AN XY: 74318

African (AFR) AF: 0.194 AC: 8069 AN: 41522

American (AMR) AF: 0.351 AC: 5363 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1320 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1387 AN: 5116

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4822

European-Finnish (FIN) AF: 0.435 AC: 4604 AN: 10572

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30965 AN: 67962

Other (OTH) AF: 0.365 AC: 770 AN: 2112

Alfa AF: 0.423 Hom.: 16843

Bravo AF: 0.348

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	-0.93
CADD	Benign	0.89
DANN	Benign	0.35
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs11711946; hg19: chr3-41287018;