rs9870255

Variant names:

• chr3-41195090-G-C
• rs9870255
• ENST00000433400.6:c.-665G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000433400.6(CTNNB1):​c.-665G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,000 control chromosomes in the GnomAD database, including 12,582 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 (12581 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: CTNNB1 ENST00000433400.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• 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)

ENSG00000233919 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• 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	ENST00000433400.6	c.-665G>C		5_prime_UTR_variant	Exon 1 of 16	4		ENSP00000387455.2
CTNNB1	ENST00000405570.6	c.-125+149G>C		intron_variant	Intron 1 of 16	2		ENSP00000385604.1
CTNNB1	ENST00000642248.1	c.-128+149G>C		intron_variant	Intron 1 of 16			ENSP00000495244.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60906 AN: 151878 Hom.: 12575 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

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) AF: 1.00 AC: 2 AN: 2

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: 0.401 AC: 60942 AN: 151996 Hom.: 12581 Cov.: 32 AF XY: 0.397 AC XY: 29495 AN XY: 74260

African (AFR) AF: 0.329 AC: 13638 AN: 41416

American (AMR) AF: 0.365 AC: 5583 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1288 AN: 5170

South Asian (SAS) AF: 0.406 AC: 1953 AN: 4812

European-Finnish (FIN) AF: 0.459 AC: 4841 AN: 10548

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30974 AN: 67972

Other (OTH) AF: 0.394 AC: 832 AN: 2112

Alfa AF: 0.418 Hom.: 1708

Bravo AF: 0.392

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.81
PhyloP100		2.8
PromoterAI		-0.0090	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs9870255; hg19: chr3-41236581;