rs2296337

chr6-33663919-G-Achr6-33663919-G-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.1148+39G>A 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 1,609,442 control chromosomes in the GnomAD database, including 69,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4866 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64994 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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 6-33663919-G-A is Benign according to our data. Variant chr6-33663919-G-A is described in ClinVar as [Benign]. Clinvar id is 1269800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.1148+39G>A		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.1148+39G>A		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.1148+39G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36574 AN: 151944 Hom.: 4863 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.286 AC: 70648 AN: 247188 Hom.: 10695 AF XY: 0.294 AC XY: 39252 AN XY: 133678

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.294 AC: 427826 AN: 1457380 Hom.: 64994 Cov.: 34 AF XY: 0.296 AC XY: 214483 AN XY: 724776

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.241

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.241 AC: 36598 AN: 152062 Hom.: 4866 Cov.: 32 AF XY: 0.245 AC XY: 18186 AN XY: 74310

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.225

Alfa AF: 0.269 Hom.: 3626

Bravo AF: 0.231

Asia WGS AF: 0.396 AC: 1376 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	1.7
Dann	Benign	0.84

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: rs2296337; hg19: chr6-33631696; COSMIC: COSV65406870;