Genetic Variant RYR1:c.-78_-55delCCCCAGCCCTCCCGCCCAGCCCGC (chr19-38433741-CCCCAGCCCGCCCCCAGCCCTCCCG-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000540.3(RYR1):c.-78_-55delCCCCAGCCCTCCCGCCCAGCCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 10 hom., cov: 28)

Exomes 𝑓: 0.00082 ( 21 hom. )

Failed GnomAD Quality Control

Consequence

RYR1
NM_000540.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 19-38433741-CCCCAGCCCGCCCCCAGCCCTCCCG-C is Benign according to our data. Variant chr19-38433741-CCCCAGCCCGCCCCCAGCCCTCCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1211621.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR1	NM_000540.3 link	c.-78_-55delCCCCAGCCCTCCCGCCCAGCCCGC		5_prime_UTR_variant	Exon 1 of 106	ENST00000359596.8	NP_000531.2	P21817-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR1	ENST00000359596 link	c.-78_-55delCCCCAGCCCTCCCGCCCAGCCCGC	5_prime_UTR_variant	Exon 1 of 106	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481 link	c.-78_-55delCCCCAGCCCTCCCGCCCAGCCCGC	5_prime_UTR_variant	Exon 1 of 105	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000599547.6 link	n.-88_-65delCCCAGCCCGCCCCCAGCCCTCCCG	upstream_gene_variant		2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

672

AN:

151666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00336

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000822

AC:

458

AN:

557210

Hom.:

AF XY:

0.000583

AC XY:

176

AN XY:

301752

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

AC:

358

AN:

16426

Gnomad4 AMR exome

AF:

0.00105

AC:

AN:

35310

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

19276

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

32554

Gnomad4 SAS exome

AF:

0.0000315

AC:

AN:

63580

Gnomad4 FIN exome

AF:

0.0000258

AC:

AN:

38750

Gnomad4 NFE exome

AF:

0.0000282

AC:

AN:

319366

Gnomad4 Remaining exome

AF:

0.00169

AC:

AN:

29566

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00450

AC:

683

AN:

151774

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

328

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.0152

AC:

0.0152386

AN:

0.0152386

Gnomad4 AMR

AF:

0.00276

AC:

0.00276352

AN:

0.00276352

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000442

AC:

0.00004418

AN:

0.00004418

Gnomad4 OTH

AF:

0.00333

AC:

0.003327

AN:

0.003327

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00342

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.00231

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 11, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=264/36

polymorphism

Splicing

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