rs7074454

Variant names:

• chr10-66105201-C-T
• rs7074454
• NM_013266.4:c.1885-1952G>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.1885-1952G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,034 control chromosomes in the GnomAD database, including 27,723 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 0.60 (27723 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 2 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

ENSG00000273360 (HGNC:):

CTNNA3-AS1 (HGNC:58344):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.1885-1952G>A		intron_variant	Intron 13 of 17	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.1885-1952G>A		intron_variant	Intron 13 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91584 AN: 151916 Hom.: 27710 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.603 AC: 91642 AN: 152034 Hom.: 27723 Cov.: 32 AF XY: 0.603 AC XY: 44838 AN XY: 74314

African (AFR) AF: 0.547 AC: 22678 AN: 41462

American (AMR) AF: 0.595 AC: 9101 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2284 AN: 3472

East Asian (EAS) AF: 0.706 AC: 3641 AN: 5156

South Asian (SAS) AF: 0.695 AC: 3350 AN: 4818

European-Finnish (FIN) AF: 0.569 AC: 6014 AN: 10572

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.625 AC: 42463 AN: 67956

Other (OTH) AF: 0.591 AC: 1246 AN: 2110

Alfa AF: 0.596 Hom.: 3567

Bravo AF: 0.601

Asia WGS AF: 0.698 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.48
PhyloP100		-0.39
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: rs7074454; hg19: chr10-67864959;