Variant 19-38489478-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.5814+35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,628 control chromosomes in the GnomAD database, including 9,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1295 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8362 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-38489478-C-G is Benign according to our data. Variant chr19-38489478-C-G is described in ClinVar as [Benign]. Clinvar id is 256529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 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.5814+35C>G		intron_variant		ENST00000359596.8	NP_000531.2	P21817-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.5814+35C>G	intron_variant	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.5814+35C>G	intron_variant	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000599547.6 linkuse as main transcript	n.5814+35C>G	intron_variant	2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18031

AN:

152072

Hom.:

1298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0870

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0430

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.0512

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0970

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.108

AC:

26711

AN:

248416

Hom.:

1849

AF XY:

0.110

AC XY:

14839

AN XY:

134476

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0931

Gnomad ASJ exome

AF:

0.0975

Gnomad EAS exome

AF:

0.0353

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.0559

Gnomad NFE exome

AF:

0.0962

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0998

AC:

145779

AN:

1460438

Hom.:

8362

Cov.:

AF XY:

0.103

AC XY:

74968

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0922

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0394

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.0551

Gnomad4 NFE exome

AF:

0.0931

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.119

AC:

18059

AN:

152190

Hom.:

1295

Cov.:

AF XY:

0.117

AC XY:

8741

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0872

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0429

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.0512

Gnomad4 NFE

AF:

0.0970

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.105

Hom.:

160

Bravo

AF:

0.120

Asia WGS

AF:

0.146

AC:

506

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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