rs2274198

Positions:

• chr6-33670880-G-A

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.2586+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,572,694 control chromosomes in the GnomAD database, including 96,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8277 hom., cov: 32)
  • Exomes 𝑓: 0.35 (88244 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.859

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=-0.85).
• BP6: Variant 6-33670880-G-A is Benign according to our data. Variant chr6-33670880-G-A is described in ClinVar as [Benign]. Clinvar id is 1177808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.2586+65G>A		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.2586+65G>A		intron_variant		1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.2586+65G>A		intron_variant		5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49867 AN: 151844 Hom.: 8256 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.349 AC: 495597 AN: 1420732 Hom.: 88244 AF XY: 0.349 AC XY: 246226 AN XY: 704872

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.329 AC: 49941 AN: 151962 Hom.: 8277 Cov.: 32 AF XY: 0.330 AC XY: 24500 AN XY: 74282

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.316

Alfa AF: 0.317 Hom.: 971

Bravo AF: 0.328

Asia WGS AF: 0.434 AC: 1509 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	-0.85
CADD	Benign	0.13
DANN	Benign	0.62

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: rs2274198; hg19: chr6-33638657;