chr3-41198686-G-A

Variant names:

• chr3-41198686-G-A
• rs3864004
• ENST00000431914.6:c.-144G>A

Variant summary

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

The ENST00000431914.6(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 ENST00000431914.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 35 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000431914.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNB1	ENST00000431914.6	TSL:4	c.-144G>A		5_prime_UTR	Exon 1 of 16	ENSP00000412219.2
	CTNNB1	ENST00000642992.1		c.-144G>A		5_prime_UTR	Exon 1 of 15	ENSP00000496385.1
	CTNNB1	ENST00000405570.6	TSL:2	c.-49+2980G>A		intron	N/A	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

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: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.382 AC: 13 AN: 34

Other (OTH) AF: 0.667 AC: 4 AN: 6

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

African (AFR) AF: 0.319 AC: 13244 AN: 41542

American (AMR) AF: 0.363 AC: 5557 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1286 AN: 5160

South Asian (SAS) AF: 0.401 AC: 1936 AN: 4822

European-Finnish (FIN) AF: 0.460 AC: 4856 AN: 10568

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30828 AN: 67992

Other (OTH) AF: 0.388 AC: 822 AN: 2116

Alfa AF: 0.435 Hom.: 25709

Bravo AF: 0.387

Asia WGS AF: 0.361 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.60
DANN	Benign	0.88
PhyloP100		-0.0060
PromoterAI		0.018	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: rs3864004; hg19: chr3-41240177;