Variant 6-33621555-C-T 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.-48C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,445,402 control chromosomes in the GnomAD database, including 2,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 231 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2592 hom. )

Consequence

ITPR3
NM_002224.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.348

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 6-33621555-C-T is Benign according to our data. Variant chr6-33621555-C-T is described in ClinVar as [Benign]. Clinvar id is 1246493.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ITPR3	NM_002224.4 linkuse as main transcript	c.-48C>T	5_prime_UTR_variant	1/58	ENST00000605930.3
ITPR3	XM_017010832.2 linkuse as main transcript	c.-37-11C>T	splice_polypyrimidine_tract_variant, intron_variant
ITPR3	XM_047418731.1 linkuse as main transcript	c.-37-11C>T	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3 linkuse as main transcript	c.-48C>T		5_prime_UTR_variant	1/58	1	NM_002224.4	P1
ITPR3	ENST00000374316.9 linkuse as main transcript	c.-48C>T		5_prime_UTR_variant	2/59	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7584

AN:

152162

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.0492

Gnomad ASJ

AF:

0.0619

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0429

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0580

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0539

AC:

8730

AN:

161968

Hom.:

310

AF XY:

0.0527

AC XY:

4534

AN XY:

86034

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.0507

Gnomad ASJ exome

AF:

0.0634

Gnomad EAS exome

AF:

0.130

Gnomad SAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.0457

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0599

AC:

77409

AN:

1293124

Hom.:

2592

Cov.:

AF XY:

0.0581

AC XY:

37415

AN XY:

644050

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.0498

Gnomad4 ASJ exome

AF:

0.0628

Gnomad4 EAS exome

AF:

0.0987

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.0498

Gnomad4 NFE exome

AF:

0.0637

Gnomad4 OTH exome

AF:

0.0646

GnomAD4 genome

AF:

0.0498

AC:

7586

AN:

152278

Hom.:

231

Cov.:

AF XY:

0.0496

AC XY:

3696

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0322

Gnomad4 AMR

AF:

0.0490

Gnomad4 ASJ

AF:

0.0619

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0429

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.0444

Alfa

AF:

0.0523

Hom.:

Bravo

AF:

0.0522

Asia WGS

AF:

0.0640

AC:

221

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

-0.48

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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