Variant 19-38444710-TC-TCC 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.631+39dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,472,310 control chromosomes in the GnomAD database, including 280,875 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27655 hom., cov: 0)

Exomes 𝑓: 0.61 ( 253220 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.767

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 -16 ACMG points.

BP6

Variant 19-38444710-T-TC is Benign according to our data. Variant chr19-38444710-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 256531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.664 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.631+39dupC		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.631+39dupC	intron_variant	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.631+39dupC	intron_variant	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000599547.6 linkuse as main transcript	n.631+39dupC	intron_variant	2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

89718

AN:

148410

Hom.:

27649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.749

Gnomad AMR

AF:

0.674

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.622

GnomAD3 exomes

AF:

0.596

AC:

127034

AN:

213030

Hom.:

38886

AF XY:

0.588

AC XY:

67805

AN XY:

115266

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.672

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.618

Gnomad SAS exome

AF:

0.396

Gnomad FIN exome

AF:

0.639

Gnomad NFE exome

AF:

0.629

Gnomad OTH exome

AF:

0.632

GnomAD4 exome

AF:

0.610

AC:

808036

AN:

1323784

Hom.:

253220

Cov.:

AF XY:

0.605

AC XY:

400779

AN XY:

662900

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.600

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.642

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.604

AC:

89757

AN:

148526

Hom.:

27655

Cov.:

AF XY:

0.600

AC XY:

43301

AN XY:

72204

show subpopulations

Gnomad4 AFR

AF:

0.517

Gnomad4 AMR

AF:

0.675

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.623

Gnomad4 SAS

AF:

0.405

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.643

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.556

Hom.:

2967

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Oct 27, 2018

- -

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