rs3748079

Positions:

• chr6-33620370-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374316.9(ITPR3):​c.-1055C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,078 control chromosomes in the GnomAD database, including 3,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3572 hom., cov: 31)
  • Exomes 𝑓: 0.26 (3 hom.)
• Consequence: ITPR3 ENST00000374316.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000374316.9	c.-1055C>T		5_prime_UTR_variant	1/59	5		P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28517 AN: 151910 Hom.: 3570 Cov.: 31

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.260 AC: 13 AN: 50 Hom.: 3 Cov.: 0 AF XY: 0.262 AC XY: 11 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.188 AC: 28521 AN: 152028 Hom.: 3572 Cov.: 31 AF XY: 0.199 AC XY: 14796 AN XY: 74288

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.159

Alfa AF: 0.180 Hom.: 296

Bravo AF: 0.166

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.3
DANN	Benign	0.89

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: rs3748079; hg19: chr6-33588147;