rs11856930

Positions:

• chr15-33736577-A-G
• chr15-33736577-A-T

Variant summary

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

The NM_001036.6(RYR3):​c.7515+252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,888 control chromosomes in the GnomAD database, including 13,915 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 0.42 (13915 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.7515+252A>G		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.7515+252A>G		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64243 AN: 151770 Hom.: 13904 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.423 AC: 64288 AN: 151888 Hom.: 13915 Cov.: 32 AF XY: 0.418 AC XY: 31003 AN XY: 74236

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.403

Alfa AF: 0.447 Hom.: 4769

Bravo AF: 0.434

Asia WGS AF: 0.260 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.66

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: rs11856930; hg19: chr15-34028778;