rs11856930

Variant names:

• chr15-33736577-A-G
• rs11856930
• NM_001036.6:c.7515+252A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

RYR3 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
• congenital myopathy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.7515+252A>G		intron_variant	Intron 49 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.7515+252A>G		intron_variant	Intron 49 of 103	1	NM_001036.6	ENSP00000489262.1

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

African (AFR) AF: 0.388 AC: 16042 AN: 41352

American (AMR) AF: 0.497 AC: 7596 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3464

East Asian (EAS) AF: 0.253 AC: 1305 AN: 5158

South Asian (SAS) AF: 0.252 AC: 1211 AN: 4808

European-Finnish (FIN) AF: 0.383 AC: 4050 AN: 10562

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31098 AN: 67958

Other (OTH) AF: 0.403 AC: 852 AN: 2112

Alfa AF: 0.441 Hom.: 7105

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
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11856930; hg19: chr15-34028778;