Variant chr19-38442480-G-A 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.270+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,568,804 control chromosomes in the GnomAD database, including 17,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1483 hom., cov: 31)

Exomes 𝑓: 0.14 ( 15791 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.365

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=-0.88).

BP6

Variant 19-38442480-G-A is Benign according to our data. Variant chr19-38442480-G-A is described in ClinVar as [Benign]. Clinvar id is 133119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38442480-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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.270+27G>A		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.270+27G>A	intron_variant	5	NM_000540.3	ENSP00000352608	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.270+27G>A	intron_variant	1		ENSP00000347667	P4	P21817-2
RYR1	ENST00000599547.6 linkuse as main transcript	c.270+27G>A	intron_variant, NMD_transcript_variant	2		ENSP00000471601

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19598

AN:

151820

Hom.:

1487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.156

AC:

38856

AN:

249018

Hom.:

3521

AF XY:

0.157

AC XY:

21147

AN XY:

134706

show subpopulations

Gnomad AFR exome

AF:

0.0995

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.143

AC:

202682

AN:

1416866

Hom.:

15791

Cov.:

AF XY:

0.144

AC XY:

102231

AN XY:

707484

show subpopulations

Gnomad4 AFR exome

AF:

0.0938

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.129

AC:

19595

AN:

151938

Hom.:

1483

Cov.:

AF XY:

0.133

AC XY:

9870

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.125

Hom.:

1102

Bravo

AF:

0.128

Asia WGS

AF:

0.303

AC:

1053

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
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 17, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

DANN

Benign

0.94

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