6-33649687-C-T

Position:

• chr6-33649687-C-T

Variant summary

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

The NM_002224.4(ITPR3):​c.161-6079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,076 control chromosomes in the GnomAD database, including 29,885 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 0.63 (29885 hom., cov: 33)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.161-6079C>T		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.161-6079C>T		intron_variant		1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.161-6079C>T		intron_variant		5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95211 AN: 151958 Hom.: 29862 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.674

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95281 AN: 152076 Hom.: 29885 Cov.: 33 AF XY: 0.624 AC XY: 46400 AN XY: 74338

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.676

Alfa AF: 0.634 Hom.: 44627

Bravo AF: 0.629

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.39

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: rs6457738; hg19: chr6-33617464;