rs3818527

Positions:

• chr6-33693258-G-A
• chr6-33693258-G-C

Variant summary

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

The NM_002224.4(ITPR3):​c.7625-287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,940 control chromosomes in the GnomAD database, including 15,658 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 0.42 (15658 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.7625-287G>A		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.7625-287G>A		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.7625-287G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63374 AN: 151822 Hom.: 15660 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.417 AC: 63385 AN: 151940 Hom.: 15658 Cov.: 32 AF XY: 0.437 AC XY: 32443 AN XY: 74280

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.398

Alfa AF: 0.371 Hom.: 2139

Bravo AF: 0.395

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.87

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: rs3818527; hg19: chr6-33661035;