rs2296339

Positions:

• chr6-33662847-C-T

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.859-64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,526,604 control chromosomes in the GnomAD database, including 192,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19470 hom., cov: 31)
  • Exomes 𝑓: 0.50 (172696 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0440

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=-0.82).
• BP6: Variant 6-33662847-C-T is Benign according to our data. Variant chr6-33662847-C-T is described in ClinVar as [Benign]. Clinvar id is 1293546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.859-64C>T		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.859-64C>T		intron_variant		1	NM_002224.4	ENSP00000475177	P1
ITPR3	ENST00000374316.9	c.859-64C>T		intron_variant		5		ENSP00000363435	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76243 AN: 151818 Hom.: 19463 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.497 AC: 683506 AN: 1374666 Hom.: 172696 Cov.: 25 AF XY: 0.495 AC XY: 335831 AN XY: 678766

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.502 AC: 76288 AN: 151938 Hom.: 19470 Cov.: 31 AF XY: 0.498 AC XY: 36980 AN XY: 74256

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.496

Alfa AF: 0.519 Hom.: 2616

Bravo AF: 0.505

Asia WGS AF: 0.296 AC: 1034 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	-0.82
CADD	Benign	2.1
DANN	Benign	0.77

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: rs2296339; hg19: chr6-33630624; COSMIC: COSV65412839;