rs11072416

Positions:

• chr15-33364511-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001036.6(RYR3):​c.51+53415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,252 control chromosomes in the GnomAD database, including 1,929 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1929 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

Genes affected

RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.51+53415A>G		intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.51+53415A>G		intron_variant		1	NM_001036.6	ENSP00000489262	P4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22025 AN: 152134 Hom.: 1931 Cov.: 32

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 22034 AN: 152252 Hom.: 1929 Cov.: 32 AF XY: 0.148 AC XY: 10989 AN XY: 74446

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.141

Alfa AF: 0.160 Hom.: 1052

Bravo AF: 0.137

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs11072416; hg19: chr15-33656712;