3-41220953-T-C

Variant names:

• chr3-41220953-T-C
• rs13072632
• NM_001904.4:c.-48-3068T>C

Variant summary

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

The NM_001904.4(CTNNB1):​c.-48-3068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,016 control chromosomes in the GnomAD database, including 12,766 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 (12766 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 25 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=-0.97).
• 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.-48-3068T>C		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.-48-3068T>C		intron_variant	Intron 1 of 14	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.-48-3068T>C		intron_variant	Intron 1 of 15			ENSP00000494845.1
CTNNB1	ENST00000715152.1	n.-48-3068T>C		intron_variant	Intron 1 of 15			ENSP00000520353.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61518 AN: 151896 Hom.: 12763 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.405 AC: 61550 AN: 152014 Hom.: 12766 Cov.: 32 AF XY: 0.401 AC XY: 29803 AN XY: 74286

African (AFR) AF: 0.343 AC: 14215 AN: 41464

American (AMR) AF: 0.368 AC: 5624 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1287 AN: 5178

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4814

European-Finnish (FIN) AF: 0.459 AC: 4836 AN: 10528

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30968 AN: 67962

Other (OTH) AF: 0.397 AC: 838 AN: 2112

Alfa AF: 0.411 Hom.: 2988

Bravo AF: 0.396

Asia WGS AF: 0.366 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.87
DANN	Benign	0.25
PhyloP100		-2.8
PromoterAI		0.019	Neutral
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: rs13072632; hg19: chr3-41262444;