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GeneBe

1-226735695-G-A

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.Ser588=) 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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.7 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
ITPKBNM_002221.4 linkuse as main transcriptc.1764C>T p.Ser588= synonymous_variant 2/8 ENST00000429204.6
ITPKBNM_001388404.1 linkuse as main transcriptc.1764C>T p.Ser588= synonymous_variant 2/3
ITPKBXM_017001211.3 linkuse as main transcriptc.1764C>T p.Ser588= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPKBENST00000429204.6 linkuse as main transcriptc.1764C>T p.Ser588= synonymous_variant 2/85 NM_002221.4 P1P27987-1
ITPKBENST00000272117.8 linkuse as main transcriptc.1764C>T p.Ser588= synonymous_variant 2/81 P1P27987-1
ITPKBENST00000366784.1 linkuse as main transcriptc.1764C>T p.Ser588= synonymous_variant 2/31 P27987-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0125
AC:
1895
AN:
152130
Hom.:
88
Cov.:
32
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.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0125
AC:
1896
AN:
152248
Hom.:
88
Cov.:
32
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.:
6
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 submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This 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.

Other links and lift over

dbSNP: rs56095953; hg19: chr1-226923396; API