rs200730524

Positions:

• chr19-38507868-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000540.3(RYR1):​c.8932+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,274,564 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (1 hom.)
• Consequence: RYR1 NM_000540.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-38507868-A-G is Benign according to our data. Variant chr19-38507868-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 256577.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3	c.8932+41A>G		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8	c.8932+41A>G		intron_variant		5	NM_000540.3	ENSP00000352608.2
RYR1	ENST00000355481.8	c.8932+41A>G		intron_variant		1		ENSP00000347667.3
RYR1	ENST00000594335.5	n.2383+41A>G		intron_variant		1		ENSP00000470927.2
RYR1	ENST00000599547.6	n.8932+41A>G		intron_variant		2		ENSP00000471601.2

Frequencies

GnomAD3 genomes AF: 0.000582 AC: 88 AN: 151244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000667

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000707

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.000632 AC: 158 AN: 249972 Hom.: 0 AF XY: 0.000651 AC XY: 88 AN XY: 135212

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00339

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000602

Gnomad NFE exome AF: 0.000841

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000828 AC: 930 AN: 1123208 Hom.: 1 Cov.: 15 AF XY: 0.000769 AC XY: 442 AN XY: 574506

Gnomad4 AFR exome AF: 0.000187

Gnomad4 AMR exome AF: 0.000159

Gnomad4 ASJ exome AF: 0.00402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000886

Gnomad4 FIN exome AF: 0.000854

Gnomad4 NFE exome AF: 0.000918

Gnomad4 OTH exome AF: 0.000610

GnomAD4 genome AF: 0.000581 AC: 88 AN: 151356 Hom.: 0 Cov.: 32 AF XY: 0.000582 AC XY: 43 AN XY: 73928

Gnomad4 AFR AF: 0.000292

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000667

Gnomad4 NFE AF: 0.000707

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.000552

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.57

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: rs200730524; hg19: chr19-38998508;