rs7554607

Positions:

• chr1-237103303-A-G
• chr1-237103303-A-T

Variant summary

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

The NM_001035.3(RYR2):​c.48+60734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,122 control chromosomes in the GnomAD database, including 12,725 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 0.41 (12725 hom., cov: 33)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.48+60734A>G		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.48+60734A>G		intron_variant		1	NM_001035.3	ENSP00000355533	P1
RYR2	ENST00000659194.3	c.48+60734A>G		intron_variant				ENSP00000499653
RYR2	ENST00000660292.2	c.48+60734A>G		intron_variant				ENSP00000499787
RYR2	ENST00000609119.2	c.48+60734A>G		intron_variant, NMD_transcript_variant		5		ENSP00000499659

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61768 AN: 152004 Hom.: 12701 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.406 AC: 61831 AN: 152122 Hom.: 12725 Cov.: 33 AF XY: 0.406 AC XY: 30146 AN XY: 74324

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.400

Alfa AF: 0.434 Hom.: 28252

Bravo AF: 0.403

Asia WGS AF: 0.319 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs7554607; hg19: chr1-237266603;