Variant rs796750554 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000540.3(RYR1):c.8068-29_8068-27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,611,506 control chromosomes in the GnomAD database, including 68,568 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9153 hom., cov: 0)

Exomes 𝑓: 0.28 ( 59415 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.613

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 -16 ACMG points.

BP6

Variant 19-38504715-ACCT-A is Benign according to our data. Variant chr19-38504715-ACCT-A is described in ClinVar as [Benign]. Clinvar id is 256570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 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.8068-29_8068-27del		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.8068-29_8068-27del	intron_variant	5	NM_000540.3	ENSP00000352608	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.8068-29_8068-27del	intron_variant	1		ENSP00000347667	P4	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	c.1520-29_1520-27del	intron_variant, NMD_transcript_variant	1		ENSP00000470927
RYR1	ENST00000599547.6 linkuse as main transcript	c.8068-29_8068-27del	intron_variant, NMD_transcript_variant	2		ENSP00000471601

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50542

AN:

151246

Hom.:

9111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.340

GnomAD3 exomes

AF:

0.324

AC:

81212

AN:

250880

Hom.:

14113

AF XY:

0.323

AC XY:

43792

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.469

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.277

AC:

403925

AN:

1460142

Hom.:

59415

AF XY:

0.281

AC XY:

204139

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.335

AC:

50643

AN:

151364

Hom.:

9153

Cov.:

AF XY:

0.341

AC XY:

25216

AN XY:

73908

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.281

Hom.:

1166

Bravo

AF:

0.343

Asia WGS

AF:

0.490

AC:

1701

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2013

- -

Congenital multicore myopathy with external ophthalmoplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2019

- -

King Denborough syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Central core myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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