chr6-33621208-C-A

Position:

• chr6-33621208-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000374316.9(ITPR3):​c.-395C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 141,474 control chromosomes in the GnomAD database, including 1,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1732 hom., cov: 30)
  • Exomes 𝑓: 0.18 (10 hom.)
• Consequence: ITPR3 ENST00000374316.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

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=-0.69).
• BP6: Variant 6-33621208-C-A is Benign according to our data. Variant chr6-33621208-C-A is described in ClinVar as [Benign]. Clinvar id is 1284184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 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.-395C>A		5_prime_UTR_variant	2/59	5		P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 19343 AN: 140946 Hom.: 1731 Cov.: 30

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00969

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.176 AC: 76 AN: 432 Hom.: 10 Cov.: 0 AF XY: 0.208 AC XY: 57 AN XY: 274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.137 AC: 19342 AN: 141042 Hom.: 1732 Cov.: 30 AF XY: 0.132 AC XY: 9085 AN XY: 68626

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.00971

Gnomad4 SAS AF: 0.0749

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.155

Alfa AF: 0.0379 Hom.: 41

Bravo AF: 0.127

Asia WGS AF: 0.0410 AC: 142 AN: 3456

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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs35329444; hg19: chr6-33588985;