rs3864004

Positions:

• chr3-41198686-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000431914(CTNNB1):​c.-144G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,228 control chromosomes in the GnomAD database, including 12,372 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 (12368 hom., cov: 34)
  • Exomes 𝑓: 0.43 (4 hom.)
• Consequence: CTNNB1 ENST00000431914 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.41198686G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000431914	c.-144G>A		5_prime_UTR_variant	1/16	4		ENSP00000412219.2
CTNNB1	ENST00000642992	c.-144G>A		5_prime_UTR_variant	1/15			ENSP00000496385.1
CTNNB1	ENST00000405570.6	c.-49+2980G>A		intron_variant		2		ENSP00000385604.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60332 AN: 152066 Hom.: 12366 Cov.: 34

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.432 AC: 19 AN: 44 Hom.: 4 Cov.: 0 AF XY: 0.423 AC XY: 11 AN XY: 26

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.397 AC: 60361 AN: 152184 Hom.: 12368 Cov.: 34 AF XY: 0.393 AC XY: 29237 AN XY: 74384

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.388

Alfa AF: 0.436 Hom.: 16264

Bravo AF: 0.387

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	-0.81
CADD	Benign	0.60
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs3864004; hg19: chr3-41240177;