Variant chr19-38502754-G-C 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.7835+27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 168 hom., cov: 13)

Exomes 𝑓: 0.0088 ( 153 hom. )

Failed GnomAD Quality Control

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.112

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=-0.81).

BP6

Variant 19-38502754-G-C is Benign according to our data. Variant chr19-38502754-G-C is described in ClinVar as [Benign]. Clinvar id is 256556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 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.7835+27G>C		intron_variant		ENST00000359596.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.7835+27G>C	intron_variant	5	NM_000540.3	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.7835+27G>C	intron_variant	1		P4	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	c.1287+27G>C	intron_variant, NMD_transcript_variant	1
RYR1	ENST00000599547.6 linkuse as main transcript	c.7835+27G>C	intron_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

3152

AN:

55860

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.00430

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000664

Gnomad OTH

AF:

0.0389

GnomAD3 exomes

AF:

0.0144

AC:

1046

AN:

72628

Hom.:

AF XY:

0.0120

AC XY:

451

AN XY:

37480

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.00832

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000571

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000727

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00876

AC:

3018

AN:

344416

Hom.:

153

Cov.:

AF XY:

0.00720

AC XY:

1313

AN XY:

182460

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.00793

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000462

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000572

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0565

AC:

3160

AN:

55896

Hom.:

168

Cov.:

AF XY:

0.0569

AC XY:

1525

AN XY:

26816

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0274

Gnomad4 ASJ

AF:

0.00430

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000664

Gnomad4 OTH

AF:

0.0382

Alfa

AF:

0.000595

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 25, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

DANN

Benign

0.74

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