rs939698

chr1-237627380-G-Achr1-237627380-G-Cchr1-237627380-G-T

Variant summary

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

The NM_001035.3(RYR2):c.6167-427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,102 control chromosomes in the GnomAD database, including 44,863 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 0.76 (44863 hom., cov: 32)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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 = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.6167-427G>A		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.6167-427G>A		intron_variant		1	NM_001035.3	P1
RYR2	ENST00000659194.3	c.6167-427G>A		intron_variant
RYR2	ENST00000660292.2	c.6167-427G>A		intron_variant
RYR2	ENST00000609119.2	c.6167-427G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115943 AN: 151984 Hom.: 44840 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.763 AC: 116002 AN: 152102 Hom.: 44863 Cov.: 32 AF XY: 0.764 AC XY: 56858 AN XY: 74386

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.760

Alfa AF: 0.808 Hom.: 99510

Bravo AF: 0.752

Asia WGS AF: 0.730 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.21
Dann	Benign	0.54

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: rs939698; hg19: chr1-237790680;