6-33668883-C-G

Position:

• chr6-33668883-C-G

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.2007-91C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,371,970 control chromosomes in the GnomAD database, including 73,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6398 hom., cov: 32)
  • Exomes 𝑓: 0.32 (66933 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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=-0.92).
• BP6: Variant 6-33668883-C-G is Benign according to our data. Variant chr6-33668883-C-G is described in ClinVar as [Benign]. Clinvar id is 1247153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.2007-91C>G		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.2007-91C>G		intron_variant		1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.2007-91C>G		intron_variant		5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42209 AN: 151986 Hom.: 6390 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.323 AC: 393561 AN: 1219866 Hom.: 66933 AF XY: 0.328 AC XY: 199692 AN XY: 608010

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.278 AC: 42238 AN: 152104 Hom.: 6398 Cov.: 32 AF XY: 0.285 AC XY: 21150 AN XY: 74336

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.273

Alfa AF: 0.277 Hom.: 807

Bravo AF: 0.262

Asia WGS AF: 0.514 AC: 1785 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.43

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: rs2296336; hg19: chr6-33636660; COSMIC: COSV65406610;