Variant chr6-33671983-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002224.4(ITPR3):c.2729-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,541,314 control chromosomes in the GnomAD database, including 361,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 36973 hom., cov: 30)

Exomes 𝑓: 0.68 ( 324245 hom. )

Consequence

ITPR3
NM_002224.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.916

Variant links:

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]

ITPR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-33671983-G-C is Benign according to our data. Variant chr6-33671983-G-C is described in ClinVar as [Benign]. Clinvar id is 1182536.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4 linkuse as main transcript	c.2729-46G>C		intron_variant		ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3 linkuse as main transcript	c.2729-46G>C		intron_variant		1	NM_002224.4	ENSP00000475177	P1
ITPR3	ENST00000374316.9 linkuse as main transcript	c.2729-46G>C		intron_variant		5		ENSP00000363435	P1

Frequencies

GnomAD3 genomes

AF:

0.694

AC:

105329

AN:

151732

Hom.:

36926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.633

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.874

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.658

GnomAD3 exomes

AF:

0.713

AC:

147801

AN:

207290

Hom.:

53465

AF XY:

0.716

AC XY:

78376

AN XY:

109450

show subpopulations

Gnomad AFR exome

AF:

0.733

Gnomad AMR exome

AF:

0.725

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.839

Gnomad SAS exome

AF:

0.860

Gnomad FIN exome

AF:

0.769

Gnomad NFE exome

AF:

0.648

Gnomad OTH exome

AF:

0.679

GnomAD4 exome

AF:

0.680

AC:

944664

AN:

1389464

Hom.:

324245

Cov.:

AF XY:

0.684

AC XY:

468973

AN XY:

685234

show subpopulations

Gnomad4 AFR exome

AF:

0.732

Gnomad4 AMR exome

AF:

0.714

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.847

Gnomad4 SAS exome

AF:

0.855

Gnomad4 FIN exome

AF:

0.761

Gnomad4 NFE exome

AF:

0.656

Gnomad4 OTH exome

AF:

0.679

GnomAD4 genome

AF:

0.694

AC:

105435

AN:

151850

Hom.:

36973

Cov.:

AF XY:

0.704

AC XY:

52225

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.726

Gnomad4 AMR

AF:

0.671

Gnomad4 ASJ

AF:

0.633

Gnomad4 EAS

AF:

0.835

Gnomad4 SAS

AF:

0.875

Gnomad4 FIN

AF:

0.774

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.662

Alfa

AF:

0.656

Hom.:

6211

Bravo

AF:

0.684

Asia WGS

AF:

0.857

AC:

2978

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.86

CADD

Benign

0.94

DANN

Benign

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over