Variant chr19-38500036-C-A 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.7323+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 1,609,466 control chromosomes in the GnomAD database, including 3,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 374 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2671 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.0980

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-38500036-C-A is Benign according to our data. Variant chr19-38500036-C-A is described in ClinVar as [Benign]. Clinvar id is 93286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38500036-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR1	NM_000540.3 linkuse as main transcript	c.7323+20C>A		intron_variant		ENST00000359596.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.7323+20C>A	intron_variant	5	NM_000540.3	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.7323+20C>A	intron_variant	1		P4	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	c.775+20C>A	intron_variant, NMD_transcript_variant	1
RYR1	ENST00000599547.6 linkuse as main transcript	c.7323+20C>A	intron_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0665

AC:

10124

AN:

152152

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0578

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0658

Gnomad ASJ

AF:

0.0956

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0575

Gnomad OTH

AF:

0.0750

GnomAD3 exomes

AF:

0.0693

AC:

17315

AN:

249882

Hom.:

715

AF XY:

0.0688

AC XY:

9305

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.0610

Gnomad AMR exome

AF:

0.0468

Gnomad ASJ exome

AF:

0.0918

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.0553

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.0568

Gnomad OTH exome

AF:

0.0800

GnomAD4 exome

AF:

0.0558

AC:

81351

AN:

1457196

Hom.:

2671

Cov.:

AF XY:

0.0564

AC XY:

40888

AN XY:

725192

show subpopulations

Gnomad4 AFR exome

AF:

0.0596

Gnomad4 AMR exome

AF:

0.0497

Gnomad4 ASJ exome

AF:

0.0949

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.0549

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.0489

Gnomad4 OTH exome

AF:

0.0637

GnomAD4 genome

AF:

0.0665

AC:

10127

AN:

152270

Hom.:

374

Cov.:

AF XY:

0.0705

AC XY:

5246

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.0655

Gnomad4 ASJ

AF:

0.0956

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.0553

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0738

Alfa

AF:

0.0461

Hom.:

Bravo

AF:

0.0631

Asia WGS

AF:

0.0980

AC:

339

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 29, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 19, 2015	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, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 07, 2013	- -

RYR1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Other:1

not provided, no classification provided

literature only

Leiden Muscular Dystrophy (RYR1)

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.0

DANN

Benign

0.55

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