Variant 19-38543746-C-G 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.11908-25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,611,652 control chromosomes in the GnomAD database, including 826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 87 hom., cov: 32)

Exomes 𝑓: 0.023 ( 739 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -1.19

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=-0.86).

BP6

Variant 19-38543746-C-G is Benign according to our data. Variant chr19-38543746-C-G is described in ClinVar as [Benign]. Clinvar id is 133024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38543746-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3 linkuse as main transcript	c.11908-25C>G		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.11908-25C>G		intron_variant		5	NM_000540.3	ENSP00000352608	A2	P21817-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3450

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00786

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.0443

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0347

AC:

8626

AN:

248910

Hom.:

279

AF XY:

0.0319

AC XY:

4301

AN XY:

134724

show subpopulations

Gnomad AFR exome

AF:

0.00731

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0474

Gnomad SAS exome

AF:

0.0309

Gnomad FIN exome

AF:

0.0445

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0230

AC:

33519

AN:

1459372

Hom.:

739

Cov.:

AF XY:

0.0227

AC XY:

16498

AN XY:

726102

show subpopulations

Gnomad4 AFR exome

AF:

0.00636

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.0293

Gnomad4 FIN exome

AF:

0.0441

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0227

AC:

3453

AN:

152280

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1888

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00782

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0597

Gnomad4 SAS

AF:

0.0329

Gnomad4 FIN

AF:

0.0443

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.00802

Hom.:

Bravo

AF:

0.0239

Asia WGS

AF:

0.0590

AC:

205

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Leiden Muscular Dystrophy (RYR1)	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.65

DANN

Benign

0.25

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