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GeneBe

1-226634824-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002221.4(ITPKB):c.2688C>T(p.Ile896=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 1,613,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 0 hom. )

Consequence

ITPKB
NM_002221.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.357
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 -9 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=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-226634824-G-A is Benign according to our data. Variant chr1-226634824-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639970.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=-0.357 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 111 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITPKBNM_002221.4 linkuse as main transcriptc.2688C>T p.Ile896= synonymous_variant 8/8 ENST00000429204.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPKBENST00000429204.6 linkuse as main transcriptc.2688C>T p.Ile896= synonymous_variant 8/85 NM_002221.4 P1P27987-1
ITPKBENST00000272117.8 linkuse as main transcriptc.2688C>T p.Ile896= synonymous_variant 8/81 P1P27987-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000729
AC:
111
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00254
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00106
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000864
AC:
217
AN:
251098
Hom.:
0
AF XY:
0.000891
AC XY:
121
AN XY:
135760
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.000794
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00278
Gnomad NFE exome
AF:
0.00113
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.000746
AC:
1090
AN:
1461346
Hom.:
0
Cov.:
30
AF XY:
0.000765
AC XY:
556
AN XY:
727012
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.000574
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.00307
Gnomad4 NFE exome
AF:
0.000757
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000729
AC:
111
AN:
152290
Hom.:
0
Cov.:
33
AF XY:
0.000739
AC XY:
55
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00254
Gnomad4 NFE
AF:
0.00106
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000885
Hom.:
0
Bravo
AF:
0.000461
EpiCase
AF:
0.000872
EpiControl
AF:
0.000889

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022ITPKB: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
6.3
Dann
Benign
0.79

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.

Other links and lift over

dbSNP: rs138300662; hg19: chr1-226822525; API