rs2960339

Positions:

• chr19-38563051-T-C

Variant summary

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

The NM_000540.3(RYR1):​c.12624+1597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,914 control chromosomes in the GnomAD database, including 11,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.38 (11853 hom., cov: 32)
• Consequence: RYR1 NM_000540.3 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.249

Genes affected

RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [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 (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3	c.12624+1597T>C		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8	c.12624+1597T>C		intron_variant		5	NM_000540.3	ENSP00000352608.2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57953 AN: 151796 Hom.: 11820 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.382 AC: 58026 AN: 151914 Hom.: 11853 Cov.: 32 AF XY: 0.383 AC XY: 28445 AN XY: 74264

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.377

Alfa AF: 0.326 Hom.: 12068

Bravo AF: 0.396

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Leiden Muscular Dystrophy (RYR1)

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.64

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: rs2960339; hg19: chr19-39053691;