rs2274200

chr6-33657919-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002224.4(ITPR3):c.283-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,611,136 control chromosomes in the GnomAD database, including 45,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3762 hom., cov: 31)
  • Exomes 𝑓: 0.23 (42135 hom.)
• Consequence: ITPR3 NM_002224.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.194

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 -10 ACMG points.

• BP6: Variant 6-33657919-T-C is Benign according to our data. Variant chr6-33657919-T-C is described in ClinVar as [Benign]. Clinvar id is 1251103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.283-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.283-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.283-13T>C		splice_polypyrimidine_tract_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30764 AN: 151790 Hom.: 3765 Cov.: 31

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.257 AC: 64141 AN: 249106 Hom.: 8932 AF XY: 0.260 AC XY: 34996 AN XY: 134664

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.291

Gnomad SAS exome AF: 0.279

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.235 AC: 342860 AN: 1459228 Hom.: 42135 Cov.: 32 AF XY: 0.238 AC XY: 172447 AN XY: 725908

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.203 AC: 30762 AN: 151908 Hom.: 3762 Cov.: 31 AF XY: 0.211 AC XY: 15639 AN XY: 74230

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.173

Alfa AF: 0.225 Hom.: 4025

Bravo AF: 0.188

Asia WGS AF: 0.220 AC: 767 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 04, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	17
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: -33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2274200; hg19: chr6-33625696; COSMIC: COSV65407076;