rs35018208

Positions:

• chr19-38444710-TC-T
• chr19-38444710-TC-TCC
• chr19-38444710-TC-TCCC

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_000540.3(RYR1):​c.631+39del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,475,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: RYR1 NM_000540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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 -1 ACMG points.

• BP6: Variant 19-38444710-TC-T is Benign according to our data. Variant chr19-38444710-TC-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR1	NM_000540.3	c.631+39del		intron_variant		ENST00000359596.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR1	ENST00000359596.8	c.631+39del		intron_variant		5	NM_000540.3	A2
RYR1	ENST00000355481.8	c.631+39del		intron_variant		1		P4
RYR1	ENST00000599547.6	c.631+39del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148680 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000426

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000751 AC: 16 AN: 213030 Hom.: 0 AF XY: 0.0000868 AC XY: 10 AN XY: 115266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000586

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000196 AC: 26 AN: 1326218 Hom.: 0 Cov.: 21 AF XY: 0.0000241 AC XY: 16 AN XY: 664104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000196

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000602

Gnomad4 OTH exome AF: 0.0000717

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 148796 Hom.: 0 Cov.: 0 AF XY: 0.0000138 AC XY: 1 AN XY: 72350

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs35018208; hg19: chr19-38935350;