rs999943

Positions:

• chr6-33656956-A-G

Variant summary

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

The NM_002224.4(ITPR3):​c.283-976A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,100 control chromosomes in the GnomAD database, including 6,278 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 0.28 (6278 hom., cov: 33)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

Genes affected

ITPR3 (HGNC:6182): (inositol 1,4,5-trisphosphate receptor type 3) This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

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 (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.283-976A>G		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.283-976A>G		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.283-976A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43037 AN: 151982 Hom.: 6277 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.283 AC: 43067 AN: 152100 Hom.: 6278 Cov.: 33 AF XY: 0.288 AC XY: 21442 AN XY: 74340

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.251

Alfa AF: 0.287 Hom.: 9346

Bravo AF: 0.276

Asia WGS AF: 0.239 AC: 834 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	2.2
DANN	Benign	0.69

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: rs999943; hg19: chr6-33624733;