Variant 1-226634679-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting

The NM_002221.4(ITPKB):c.2833C>G(p.Leu945Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 826,106 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

ITPKB
NM_002221.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

ITPKB (HGNC:6179): (inositol-trisphosphate 3-kinase B) The protein encoded by this protein regulates inositol phosphate metabolism by phosphorylation of second messenger inositol 1,4,5-trisphosphate to Ins(1,3,4,5)P4. The activity of this encoded protein is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. [provided by RefSeq, Jul 2008]

ITPKB links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039837062).

BP6

Variant 1-226634679-G-C is Benign according to our data. Variant chr1-226634679-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3038080.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 208 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKB	NM_002221.4 link	c.2833C>G	p.Leu945Val	missense_variant	8/8	ENST00000429204.6	NP_002212.3	P27987-1B2R9J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKB	ENST00000429204.6 link	c.2833C>G	p.Leu945Val	missense_variant	8/8	5	NM_002221.4	ENSP00000411152.1		P27987-1
ITPKB	ENST00000272117.8 link	c.2833C>G	p.Leu945Val	missense_variant	8/8	1		ENSP00000272117.3		P27987-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00184

AC:

461

AN:

250178

Hom.:

AF XY:

0.00208

AC XY:

281

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00334

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00203

AC:

1370

AN:

673792

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

794

AN XY:

364148

show subpopulations

Gnomad4 AFR exome

AF:

0.000433

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.0000471

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00367

Gnomad4 FIN exome

AF:

0.000923

Gnomad4 NFE exome

AF:

0.00256

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152314

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00195

AC:

237

EpiCase

AF:

0.00316

EpiControl

AF:

0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ITPKB-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.013

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.012

B;B

Vest4

0.029

MVP

0.25

MPC

1.5

ClinPred

0.018

GERP RS

2.0

Varity_R

0.11

gMVP

0.35

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