rs1786912

Variant names:

• chr10-65961722-A-T
• rs1786912
• NM_013266.4:c.2400+4890T>A

Variant summary

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

The NM_013266.4(CTNNA3):​c.2400+4890T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,888 control chromosomes in the GnomAD database, including 1,782 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 0.14 (1782 hom., cov: 30)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 4 publications found

Genes affected

CTNNA3 (HGNC:2511): (catenin alpha 3) This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

CTNNA3 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.2400+4890T>A		intron_variant	Intron 17 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.2400+4890T>A		intron_variant	Intron 17 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21597 AN: 151770 Hom.: 1778 Cov.: 30

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.142 AC: 21620 AN: 151888 Hom.: 1782 Cov.: 30 AF XY: 0.150 AC XY: 11117 AN XY: 74220

African (AFR) AF: 0.0981 AC: 4068 AN: 41458

American (AMR) AF: 0.185 AC: 2819 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.174 AC: 891 AN: 5126

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4814

European-Finnish (FIN) AF: 0.256 AC: 2699 AN: 10532

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8989 AN: 67930

Other (OTH) AF: 0.136 AC: 287 AN: 2104

Alfa AF: 0.141 Hom.: 210

Bravo AF: 0.135

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.73
PhyloP100		-1.3
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: rs1786912; hg19: chr10-67721480;