Variant chr1-226735695-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_002221.4(ITPKB):c.1764C>T(p.Ser588Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00989 in 1,597,684 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 622 hom. )

Consequence

ITPKB
NM_002221.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.70

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 1-226735695-G-A is Benign according to our data. Variant chr1-226735695-G-A is described in ClinVar as [Benign]. Clinvar id is 2688336.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKB	NM_002221.4 link	c.1764C>T	p.Ser588Ser	synonymous_variant	2/8	ENST00000429204.6	NP_002212.3	P27987-1B2R9J0
ITPKB	NM_001388404.1 link	c.1764C>T	p.Ser588Ser	synonymous_variant	2/3		NP_001375333.1
ITPKB	XM_017001211.3 link	c.1764C>T	p.Ser588Ser	synonymous_variant	2/3		XP_016856700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITPKB	ENST00000429204.6 link	c.1764C>T	p.Ser588Ser	synonymous_variant	2/8	5	NM_002221.4	ENSP00000411152.1	P27987-1
ITPKB	ENST00000272117.8 link	c.1764C>T	p.Ser588Ser	synonymous_variant	2/8	1		ENSP00000272117.3	P27987-1
ITPKB	ENST00000366784.1 link	c.1764C>T	p.Ser588Ser	synonymous_variant	2/3	1		ENSP00000355748.1	P27987-2

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1895

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0718

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0284

AC:

6720

AN:

236852

Hom.:

313

AF XY:

0.0266

AC XY:

3405

AN XY:

128156

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.00116

Gnomad EAS exome

AF:

0.0711

Gnomad SAS exome

AF:

0.0617

Gnomad FIN exome

AF:

0.00109

Gnomad NFE exome

AF:

0.000594

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.00962

AC:

13906

AN:

1445436

Hom.:

622

Cov.:

AF XY:

0.0107

AC XY:

7655

AN XY:

717384

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.000877

Gnomad4 EAS exome

AF:

0.0724

Gnomad4 SAS exome

AF:

0.0611

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.000505

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0125

AC:

1896

AN:

152248

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1083

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.0706

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0719

Gnomad4 SAS

AF:

0.0622

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.2

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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