Variant rs45555835 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.11907+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,612,706 control chromosomes in the GnomAD database, including 1,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 274 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1716 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.182

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=-0.85).

BP6

Variant 19-38543682-G-A is Benign according to our data. Variant chr19-38543682-G-A is described in ClinVar as [Benign]. Clinvar id is 256413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38543682-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0511 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.11907+22G>A		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.11907+22G>A		intron_variant		5	NM_000540.3	ENSP00000352608	A2	P21817-1

Frequencies

GnomAD3 genomes

AF:

0.0543

AC:

8267

AN:

152116

Hom.:

273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0543

Gnomad ASJ

AF:

0.0812

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0614

GnomAD3 exomes

AF:

0.0494

AC:

12331

AN:

249824

Hom.:

413

AF XY:

0.0493

AC XY:

6665

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.0499

Gnomad AMR exome

AF:

0.0298

Gnomad ASJ exome

AF:

0.0756

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0352

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.0509

Gnomad OTH exome

AF:

0.0598

GnomAD4 exome

AF:

0.0447

AC:

65282

AN:

1460472

Hom.:

1716

Cov.:

AF XY:

0.0449

AC XY:

32621

AN XY:

726566

show subpopulations

Gnomad4 AFR exome

AF:

0.0529

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.0787

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0353

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.0427

Gnomad4 OTH exome

AF:

0.0490

GnomAD4 genome

AF:

0.0544

AC:

8274

AN:

152234

Hom.:

274

Cov.:

AF XY:

0.0579

AC XY:

4312

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0507

Gnomad4 AMR

AF:

0.0542

Gnomad4 ASJ

AF:

0.0812

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0352

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0603

Alfa

AF:

0.0567

Hom.:

Bravo

AF:

0.0512

Asia WGS

AF:

0.0200

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 26, 2018	- -
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 29, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.0

DANN

Benign

0.81

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