rs2441718

Variant names:

• chr10-66377203-A-G
• rs2441718
• NM_013266.4:c.1732+1949T>C

Variant summary

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

The NM_013266.4(CTNNA3):​c.1732+1949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,962 control chromosomes in the GnomAD database, including 7,373 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 0.31 (7373 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1732+1949T>C		intron	N/A	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.1732+1949T>C		intron	N/A	NP_001120856.1	Q9UI47-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1732+1949T>C		intron	N/A	ENSP00000389714.1	Q9UI47-1
	CTNNA3	ENST00000682758.1		c.1732+1949T>C		intron	N/A	ENSP00000508047.1	Q9UI47-1
	CTNNA3	ENST00000684154.1		c.1732+1949T>C		intron	N/A	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46990 AN: 151844 Hom.: 7373 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.309 AC: 46997 AN: 151962 Hom.: 7373 Cov.: 32 AF XY: 0.306 AC XY: 22766 AN XY: 74278

African (AFR) AF: 0.313 AC: 13001 AN: 41480

American (AMR) AF: 0.247 AC: 3770 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3470

East Asian (EAS) AF: 0.164 AC: 851 AN: 5174

South Asian (SAS) AF: 0.346 AC: 1666 AN: 4818

European-Finnish (FIN) AF: 0.298 AC: 3151 AN: 10566

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21910 AN: 67884

Other (OTH) AF: 0.333 AC: 701 AN: 2108

Alfa AF: 0.318 Hom.: 12379

Bravo AF: 0.302

Asia WGS AF: 0.255 AC: 890 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.51
PhyloP100		0.81
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: rs2441718; hg19: chr10-68136961;