19-38433741-CCCCAGCCCGCCCCCAGCCCTCCCG-C

Position:

• chr19-38433741-CCCCAGCCCGCCCCCAGCCCTCCCG-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000540.3(RYR1):​c.-78_-55del 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.43

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]

ACMG classification

Verdict is Likely_benign. Variant got -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/exons	MANE	Protein	UniProt
RYR1	NM_000540.3	c.-78_-55del		5_prime_UTR_variant	1/106	ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8	c.-78_-55del		5_prime_UTR_variant	1/106	5	NM_000540.3	ENSP00000352608	A2
RYR1	ENST00000355481.8	c.-78_-55del		5_prime_UTR_variant	1/105	1		ENSP00000347667	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 672 AN: 151666 Hom.: 8 Cov.: 28 FAILED QC

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.: 21 AF XY: 0.000583 AC XY: 176 AN XY: 301752

Gnomad4 AFR exome AF: 0.0218

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000315

Gnomad4 FIN exome AF: 0.0000258

Gnomad4 NFE exome AF: 0.0000282

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00450 AC: 683 AN: 151774 Hom.: 10 Cov.: 28 AF XY: 0.00442 AC XY: 328 AN XY: 74174

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.00276

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00333

Alfa AF: 0.00342 Hom.: 0

Bravo AF: 0.00541

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs573058662; hg19: chr19-38924381;