rs2296343

Positions:

• chr6-33658940-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002224.4(ITPR3):​c.529-81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,598,006 control chromosomes in the GnomAD database, including 70,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4728 hom., cov: 32)
  • Exomes 𝑓: 0.29 (65407 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-33658940-T-C is Benign according to our data. Variant chr6-33658940-T-C is described in ClinVar as [Benign]. Clinvar id is 1251010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.529-81T>C		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.529-81T>C		intron_variant		1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.529-81T>C		intron_variant		5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35042 AN: 151968 Hom.: 4728 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.295 AC: 425982 AN: 1445920 Hom.: 65407 Cov.: 29 AF XY: 0.298 AC XY: 213918 AN XY: 718986

Gnomad4 AFR exome AF: 0.0917

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.231 AC: 35057 AN: 152086 Hom.: 4728 Cov.: 32 AF XY: 0.235 AC XY: 17430 AN XY: 74326

Gnomad4 AFR AF: 0.0990

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.214

Alfa AF: 0.280 Hom.: 10032

Bravo AF: 0.218

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.47
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2296343; hg19: chr6-33626717; COSMIC: COSV65409459;