1-237186438-T-C

Position:

• chr1-237186438-T-C

Variant summary

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

The NM_001035.3(RYR2):​c.49-84059T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,072 control chromosomes in the GnomAD database, including 20,098 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 0.51 (20098 hom., cov: 33)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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 (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.49-84059T>C		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.49-84059T>C		intron_variant		1	NM_001035.3	ENSP00000355533	P1
RYR2	ENST00000659194.3	c.49-84059T>C		intron_variant				ENSP00000499653
RYR2	ENST00000660292.2	c.49-84059T>C		intron_variant				ENSP00000499787
RYR2	ENST00000609119.2	c.49-84059T>C		intron_variant, NMD_transcript_variant		5		ENSP00000499659

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77538 AN: 151954 Hom.: 20084 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.510 AC: 77591 AN: 152072 Hom.: 20098 Cov.: 33 AF XY: 0.508 AC XY: 37745 AN XY: 74342

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.524

Alfa AF: 0.480 Hom.: 29687

Bravo AF: 0.517

Asia WGS AF: 0.563 AC: 1961 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	2.7
DANN	Benign	0.68

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: rs6683225; hg19: chr1-237349738;