rs6901411

Positions:

• chr6-33665750-A-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.1410-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,488,066 control chromosomes in the GnomAD database, including 66,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4951 hom., cov: 32)
  • Exomes 𝑓: 0.30 (61109 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.667

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=-0.9).
• BP6: Variant 6-33665750-A-G is Benign according to our data. Variant chr6-33665750-A-G is described in ClinVar as [Benign]. Clinvar id is 1293549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.1410-85A>G		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.1410-85A>G		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.1410-85A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36794 AN: 151866 Hom.: 4948 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.296 AC: 395953 AN: 1336082 Hom.: 61109 AF XY: 0.300 AC XY: 198898 AN XY: 663932

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.242 AC: 36819 AN: 151984 Hom.: 4951 Cov.: 32 AF XY: 0.247 AC XY: 18326 AN XY: 74278

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.230

Alfa AF: 0.266 Hom.: 4691

Bravo AF: 0.232

Asia WGS AF: 0.408 AC: 1417 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	-0.90
CADD	Benign	1.1
DANN	Benign	0.64

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: rs6901411; hg19: chr6-33633527; COSMIC: COSV65412842;