rs1798802

Positions:

• chr3-41220488-A-G
• chr3-41220488-A-T

Variant summary

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

The ENST00000349496.11(CTNNB1):​c.-48-3533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 149,700 control chromosomes in the GnomAD database, including 15,096 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 0.43 (15096 hom., cov: 26)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CTNNB1 ENST00000349496.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.-48-3533A>G		intron_variant		ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.-48-3533A>G		intron_variant		1	NM_001904.4	ENSP00000344456	P4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 64783 AN: 149582 Hom.: 15094 Cov.: 26

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.466

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

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.433 AC: 64797 AN: 149698 Hom.: 15096 Cov.: 26 AF XY: 0.435 AC XY: 31687 AN XY: 72912

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.468

Alfa AF: 0.489 Hom.: 8798

Bravo AF: 0.414

Asia WGS AF: 0.545 AC: 1890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.75

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: rs1798802; hg19: chr3-41261979;