rs1786909

Variant names:

• chr10-65940412-A-C
• rs1786909
• NM_013266.4:c.2401-19795T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-65940412-A-C
• chr10-65940412-A-T

Variant summary

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

The NM_013266.4(CTNNA3):​c.2401-19795T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,112 control chromosomes in the GnomAD database, including 48,726 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 0.80 (48726 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.2401-19795T>G		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.2401-19795T>G		intron_variant	Intron 17 of 17	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121371 AN: 151994 Hom.: 48680 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.799 AC: 121472 AN: 152112 Hom.: 48726 Cov.: 32 AF XY: 0.799 AC XY: 59436 AN XY: 74364

African (AFR) AF: 0.843 AC: 34993 AN: 41516

American (AMR) AF: 0.840 AC: 12821 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2841 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3901 AN: 5168

South Asian (SAS) AF: 0.756 AC: 3640 AN: 4816

European-Finnish (FIN) AF: 0.818 AC: 8651 AN: 10574

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51914 AN: 67978

Other (OTH) AF: 0.819 AC: 1733 AN: 2116

Alfa AF: 0.776 Hom.: 175825

Bravo AF: 0.804

Asia WGS AF: 0.789 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.070
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: rs1786909; hg19: chr10-67700170;