rs747073959

Positions:

• chr19-38505982-AT-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000540.3(RYR1):​c.8541+37delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,403,984 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.00015 (10 hom.)
• Consequence: RYR1 NM_000540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3	c.8541+37delT		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8	c.8541+37delT		intron_variant		5	NM_000540.3	ENSP00000352608.2
RYR1	ENST00000355481.8	c.8541+37delT		intron_variant		1		ENSP00000347667.3
RYR1	ENST00000594335.5	n.1992+37delT		intron_variant		1		ENSP00000470927.2
RYR1	ENST00000599547.6	n.8541+37delT		intron_variant		2		ENSP00000471601.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.000147 AC: 207 AN: 1403984 Hom.: 10 Cov.: 32 AF XY: 0.000127 AC XY: 89 AN XY: 699730

Gnomad4 AFR exome AF: 0.000193

Gnomad4 AMR exome AF: 0.0000228

Gnomad4 ASJ exome AF: 0.000197

Gnomad4 EAS exome AF: 0.000131

Gnomad4 SAS exome AF: 0.0000599

Gnomad4 FIN exome AF: 0.0000601

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.000190

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs747073959; hg19: chr19-38996622;