rs12410114

Positions:

• chr1-237607791-T-A
• chr1-237607791-T-C
• chr1-237607791-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001035.3(RYR2):​c.4684-2971T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,980 control chromosomes in the GnomAD database, including 27,287 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 0.55 (27287 hom., cov: 32)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54

Genes affected

RYR2 (HGNC:10484): (ryanodine receptor 2) This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.4684-2971T>A		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.4684-2971T>A		intron_variant		1	NM_001035.3	ENSP00000355533	P1
RYR2	ENST00000659194.3	c.4684-2971T>A		intron_variant				ENSP00000499653
RYR2	ENST00000660292.2	c.4684-2971T>A		intron_variant				ENSP00000499787
RYR2	ENST00000609119.2	c.4684-2971T>A		intron_variant, NMD_transcript_variant		5		ENSP00000499659

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84262 AN: 151862 Hom.: 27277 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.555 AC: 84299 AN: 151980 Hom.: 27287 Cov.: 32 AF XY: 0.555 AC XY: 41247 AN XY: 74264

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.597

Alfa AF: 0.509 Hom.: 1740

Bravo AF: 0.543

Asia WGS AF: 0.492 AC: 1711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.038
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs12410114; hg19: chr1-237771091; COSMIC: COSV63673780;