Variant 1-226637640-G-A 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_002221.4(ITPKB):c.2625+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,498,536 control chromosomes in the GnomAD database, including 13,851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1897 hom., cov: 33)

Exomes 𝑓: 0.13 ( 11954 hom. )

Consequence

ITPKB
NM_002221.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.36

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:

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=-0.87).

BP6

Variant 1-226637640-G-A is Benign according to our data. Variant chr1-226637640-G-A is described in ClinVar as [Benign]. Clinvar id is 2688311.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPKB	NM_002221.4 linkuse as main transcript	c.2625+39C>T		intron_variant		ENST00000429204.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPKB	ENST00000429204.6 linkuse as main transcript	c.2625+39C>T		intron_variant		5	NM_002221.4	P1	P27987-1
ITPKB	ENST00000272117.8 linkuse as main transcript	c.2625+39C>T		intron_variant		1		P1	P27987-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22964

AN:

152158

Hom.:

1895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.151

AC:

37005

AN:

245464

Hom.:

3082

AF XY:

0.148

AC XY:

19600

AN XY:

132592

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.279

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.126

AC:

169681

AN:

1346258

Hom.:

11954

Cov.:

AF XY:

0.126

AC XY:

85339

AN XY:

675852

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.151

AC:

22982

AN:

152278

Hom.:

1897

Cov.:

AF XY:

0.154

AC XY:

11448

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.129

Hom.:

1896

Bravo

AF:

0.160

Asia WGS

AF:

0.210

AC:

736

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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

0.27

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

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