3-41235549-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001904.4(CTNNB1):c.1684-175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 759,648 control chromosomes in the GnomAD database, including 62,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9883 hom., cov: 31)
  • Exomes 𝑓: 0.41 (52784 hom.)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.855

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-41235549-C-T is Benign according to our data. Variant chr3-41235549-C-T is described in ClinVar as [Benign]. Clinvar id is 1223535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNB1	NM_001904.4	c.1684-175C>T		intron_variant		ENST00000349496.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNB1	ENST00000349496.11	c.1684-175C>T		intron_variant		1	NM_001904.4	P4

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50747 AN: 151832 Hom.: 9885 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.406 AC: 246933 AN: 607698 Hom.: 52784 Cov.: 8 AF XY: 0.404 AC XY: 130486 AN XY: 322904

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.394

GnomAD4 genome AF: 0.334 AC: 50746 AN: 151950 Hom.: 9883 Cov.: 31 AF XY: 0.332 AC XY: 24685 AN XY: 74286

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.339

Alfa AF: 0.343 Hom.: 1484

Bravo AF: 0.316

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.8
Dann	Benign	0.81

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: rs11564465; hg19: chr3-41277040;