Variant 19-38586613-G-T 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.15021+37G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,593,966 control chromosomes in the GnomAD database, including 5,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 401 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5517 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.96

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 19-38586613-G-T is Benign according to our data. Variant chr19-38586613-G-T is described in ClinVar as [Benign]. Clinvar id is 256455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0904 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.15021+37G>T		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.15021+37G>T		intron_variant		5	NM_000540.3	ENSP00000352608	A2	P21817-1

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

9255

AN:

152098

Hom.:

401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.0359

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0923

Gnomad OTH

AF:

0.0498

GnomAD3 exomes

AF:

0.0621

AC:

15610

AN:

251190

Hom.:

648

AF XY:

0.0629

AC XY:

8541

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0325

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0901

Gnomad OTH exome

AF:

0.0667

GnomAD4 exome

AF:

0.0823

AC:

118620

AN:

1441750

Hom.:

5517

Cov.:

AF XY:

0.0810

AC XY:

58209

AN XY:

718586

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0303

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0344

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.0938

Gnomad4 OTH exome

AF:

0.0704

GnomAD4 genome

AF:

0.0608

AC:

9253

AN:

152216

Hom.:

401

Cov.:

AF XY:

0.0595

AC XY:

4431

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0359

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0310

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.0923

Gnomad4 OTH

AF:

0.0492

Alfa

AF:

0.0640

Hom.:

147

Bravo

AF:

0.0537

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.013

DANN

Benign

0.44

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