rs2140090

Variant names:

• chr3-41213155-G-T
• rs2140090
• NM_001904.4:c.-48-10866G>T

Variant summary

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

The NM_001904.4(CTNNB1):​c.-48-10866G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,998 control chromosomes in the GnomAD database, including 12,317 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 (12317 hom., cov: 32)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.-48-10866G>T		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.-48-10866G>T		intron_variant	Intron 1 of 14	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.-48-10866G>T		intron_variant	Intron 1 of 15			ENSP00000494845.1
CTNNB1	ENST00000715152.1	n.-48-10866G>T		intron_variant	Intron 1 of 15			ENSP00000520353.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60210 AN: 151880 Hom.: 12315 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.396 AC: 60231 AN: 151998 Hom.: 12317 Cov.: 32 AF XY: 0.393 AC XY: 29182 AN XY: 74284

African (AFR) AF: 0.316 AC: 13077 AN: 41444

American (AMR) AF: 0.365 AC: 5575 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1285 AN: 5174

South Asian (SAS) AF: 0.405 AC: 1949 AN: 4816

European-Finnish (FIN) AF: 0.460 AC: 4857 AN: 10548

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

European-Non Finnish (NFE) AF: 0.454 AC: 30845 AN: 67958

Other (OTH) AF: 0.389 AC: 821 AN: 2110

Alfa AF: 0.413 Hom.: 4941

Bravo AF: 0.386

Asia WGS AF: 0.362 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		-0.11
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: rs2140090; hg19: chr3-41254646;