rs11564445

Variant names:

• chr3-41226261-C-T
• rs11564445
• NM_001904.4:c.936+400C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001904.4(CTNNB1):​c.936+400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 152,228 control chromosomes in the GnomAD database, including 134 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 0.031 (134 hom., cov: 32)
• Consequence: CTNNB1 NM_001904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 11 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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0309 (4698/152228) while in subpopulation NFE AF = 0.0451 (3065/68022). AF 95% confidence interval is 0.0437. There are 134 homozygotes in GnomAd4. There are 2319 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4698 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.936+400C>T		intron_variant	Intron 6 of 14	ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.936+400C>T		intron_variant	Intron 6 of 14	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.936+400C>T		intron_variant	Intron 6 of 15			ENSP00000494845.1
CTNNB1	ENST00000715152.1	n.936+400C>T		intron_variant	Intron 6 of 15			ENSP00000520353.1

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4697 AN: 152110 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0309 AC: 4698 AN: 152228 Hom.: 134 Cov.: 32 AF XY: 0.0312 AC XY: 2319 AN XY: 74420

African (AFR) AF: 0.00645 AC: 268 AN: 41540

American (AMR) AF: 0.0176 AC: 269 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4824

European-Finnish (FIN) AF: 0.0811 AC: 858 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3065 AN: 68022

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0388 Hom.: 464

Bravo AF: 0.0239

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.43
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism

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: rs11564445; hg19: chr3-41267752;