Variant rs4802583 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000540.3(RYR1):c.11260-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,608,738 control chromosomes in the GnomAD database, including 802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 92 hom., cov: 31)

Exomes 𝑓: 0.023 ( 710 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.669

Variant links:

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]

RYR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 19-38534701-T-G is Benign according to our data. Variant chr19-38534701-T-G is described in ClinVar as [Benign]. Clinvar id is 167623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38534701-T-G is described in Lovd as [Likely_benign]. Variant chr19-38534701-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3 link	c.11260-19T>G		intron_variant		ENST00000359596.8	NP_000531.2	P21817-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8 link	c.11260-19T>G		intron_variant		5	NM_000540.3	ENSP00000352608.2		P21817-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3449

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00777

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0724

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0598

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0240

GnomAD3 exomes

AF:

0.0344

AC:

8464

AN:

246320

Hom.:

282

AF XY:

0.0317

AC XY:

4224

AN XY:

133194

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.0473

Gnomad SAS exome

AF:

0.0302

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0227

AC:

33071

AN:

1456456

Hom.:

710

Cov.:

AF XY:

0.0225

AC XY:

16276

AN XY:

724426

show subpopulations

Gnomad4 AFR exome

AF:

0.00632

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.00227

Gnomad4 EAS exome

AF:

0.0685

Gnomad4 SAS exome

AF:

0.0286

Gnomad4 FIN exome

AF:

0.0440

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0227

AC:

3452

AN:

152282

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1888

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00772

Gnomad4 AMR

AF:

0.0726

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0597

Gnomad4 SAS

AF:

0.0329

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0222

Hom.:

Bravo

AF:

0.0239

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 22, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

RYR1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over