Variant 19-38528513-A-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.10938-86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,589,218 control chromosomes in the GnomAD database, including 21,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1907 hom., cov: 31)

Exomes 𝑓: 0.16 ( 19431 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.675

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:

(HGNC:):

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=-0.9).

BP6

Variant 19-38528513-A-G is Benign according to our data. Variant chr19-38528513-A-G is described in ClinVar as [Benign]. Clinvar id is 133002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38528513-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR1	NM_000540.3 linkuse as main transcript	c.10938-86A>G		intron_variant		ENST00000359596.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.10938-86A>G		intron_variant		5	NM_000540.3	A2	P21817-1
	ENST00000597015.1 linkuse as main transcript	n.43T>C		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22880

AN:

151860

Hom.:

1896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.156

AC:

224574

AN:

1437240

Hom.:

19431

Cov.:

AF XY:

0.159

AC XY:

114209

AN XY:

716108

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.151

AC:

22930

AN:

151978

Hom.:

1907

Cov.:

AF XY:

0.154

AC XY:

11436

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.0557

Hom.:

Bravo

AF:

0.153

Asia WGS

AF:

0.324

AC:

1124

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
not provided, no classification provided	literature only	Leiden Muscular Dystrophy (RYR1)	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.52

DANN

Benign

0.28

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