1-237725555-T-A

Position:

• chr1-237725555-T-A

Variant summary

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

The NM_001035.3(RYR2):​c.10690-718T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,938 control chromosomes in the GnomAD database, including 24,781 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 0.54 (24781 hom., cov: 32)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.10690-718T>A		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.10690-718T>A		intron_variant		1	NM_001035.3	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82254 AN: 151820 Hom.: 24785 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.541 AC: 82254 AN: 151938 Hom.: 24781 Cov.: 32 AF XY: 0.543 AC XY: 40316 AN XY: 74244

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.555

Alfa AF: 0.509 Hom.: 1715

Bravo AF: 0.519

Asia WGS AF: 0.474 AC: 1647 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.31

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: rs2819774; hg19: chr1-237888855;