rs11564465

Variant names:

• chr3-41235549-C-A
• rs11564465
• NM_001904.4:c.1684-175C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-41235549-C-A
• chr3-41235549-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001904.4(CTNNB1):​c.1684-175C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 608,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• Publications: 17 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.1684-175C>A		intron_variant	Intron 10 of 14	ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.1684-175C>A		intron_variant	Intron 10 of 14	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.1684-175C>A		intron_variant	Intron 10 of 15			ENSP00000494845.1
CTNNB1	ENST00000715152.1	n.1684-175C>A		intron_variant	Intron 10 of 15			ENSP00000520353.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000164 AC: 1 AN: 608900 Hom.: 0 Cov.: 8 AF XY: 0.00000309 AC XY: 1 AN XY: 323512

African (AFR) AF: 0.00 AC: 0 AN: 16646

American (AMR) AF: 0.00 AC: 0 AN: 32980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17966

East Asian (EAS) AF: 0.00 AC: 0 AN: 31832

South Asian (SAS) AF: 0.00 AC: 0 AN: 58008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2426

European-Non Finnish (NFE) AF: 0.00000260 AC: 1 AN: 385040

Other (OTH) AF: 0.00 AC: 0 AN: 31684

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.83
PhyloP100		-0.85

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: rs11564465; hg19: chr3-41277040;