rs4711336

Positions:

• chr6-33691269-G-A
• chr6-33691269-G-C

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.7225+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,986 control chromosomes in the GnomAD database, including 16,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (16889 hom., cov: 32)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367

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=-0.87).
• BP6: Variant 6-33691269-G-A is Benign according to our data. Variant chr6-33691269-G-A is described in ClinVar as [Benign]. Clinvar id is 1238783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.7225+160G>A		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.7225+160G>A		intron_variant		1	NM_002224.4	ENSP00000475177	P1
ITPR3	ENST00000374316.9	c.7225+160G>A		intron_variant		5		ENSP00000363435	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65935 AN: 151880 Hom.: 16879 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.434 AC: 65959 AN: 151986 Hom.: 16889 Cov.: 32 AF XY: 0.454 AC XY: 33715 AN XY: 74274

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.421

Alfa AF: 0.454 Hom.: 2852

Bravo AF: 0.410

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	-0.87
CADD	Benign	2.5
DANN	Benign	0.71

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: rs4711336; hg19: chr6-33659046;