Variant 19-38507857-G-GC 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.8932+34dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8550 hom., cov: 0)

Exomes 𝑓: 0.27 ( 49339 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.483

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 19-38507857-G-GC is Benign according to our data. Variant chr19-38507857-G-GC is described in ClinVar as [Benign]. Clinvar id is 256576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 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.8932+34dup		intron_variant		ENST00000359596.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.8932+34dup	intron_variant	5	NM_000540.3	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.8932+34dup	intron_variant	1		P4	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	c.2384+34dup	intron_variant, NMD_transcript_variant	1
RYR1	ENST00000599547.6 linkuse as main transcript	c.8932+34dup	intron_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49168

AN:

151454

Hom.:

8514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.333

GnomAD3 exomes

AF:

0.322

AC:

80321

AN:

249778

Hom.:

13798

AF XY:

0.322

AC XY:

43433

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.437

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.270

AC:

329869

AN:

1223892

Hom.:

49339

Cov.:

AF XY:

0.276

AC XY:

171019

AN XY:

620590

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.387

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.325

AC:

49265

AN:

151572

Hom.:

8550

Cov.:

AF XY:

0.332

AC XY:

24565

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.429

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.256

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.275

Hom.:

1092

Bravo

AF:

0.331

Asia WGS

AF:

0.487

AC:

1692

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2013

- -

Congenital multicore myopathy with external ophthalmoplegia

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

- -

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

- -

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