ENST00000559457.2:n.215C>A

Variant names:

• chr15-33306336-G-T
• rs2251110
• ENST00000559457.2:n.215C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000559457.2(RYR3-DT):​n.215C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,926 control chromosomes in the GnomAD database, including 18,624 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 0.49 (18624 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: RYR3-DT ENST00000559457.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 10 publications found

Genes affected

RYR3-DT (HGNC:51417): (RYR3 divergent transcript)

ENSG00000293377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000559457.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3-DT	NR_120326.1		n.192C>A		non_coding_transcript_exon	Exon 2 of 3
	RYR3-DT	NR_120327.1		n.178C>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3-DT	ENST00000559457.2	TSL:3	n.215C>A		non_coding_transcript_exon	Exon 2 of 3
	RYR3-DT	ENST00000561458.6	TSL:2	n.502C>A		non_coding_transcript_exon	Exon 2 of 3
	RYR3-DT	ENST00000666561.1		n.311C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74851 AN: 151808 Hom.: 18634 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.515

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.493 AC: 74858 AN: 151926 Hom.: 18624 Cov.: 33 AF XY: 0.494 AC XY: 36699 AN XY: 74218

African (AFR) AF: 0.458 AC: 18969 AN: 41422

American (AMR) AF: 0.479 AC: 7311 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2561 AN: 5168

South Asian (SAS) AF: 0.518 AC: 2486 AN: 4802

European-Finnish (FIN) AF: 0.508 AC: 5337 AN: 10512

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34658 AN: 67972

Other (OTH) AF: 0.513 AC: 1082 AN: 2108

Alfa AF: 0.502 Hom.: 29669

Bravo AF: 0.490

Asia WGS AF: 0.492 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.64
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs2251110; hg19: chr15-33598537;