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GeneBe

1-226735563-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.1896C>T(p.Ala632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,547,646 control chromosomes in the GnomAD database, including 61,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6046 hom., cov: 32)
Exomes 𝑓: 0.28 ( 55557 hom. )

Consequence

ITPKB
NM_002221.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.12
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=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-226735563-G-A is Benign according to our data. Variant chr1-226735563-G-A is described in ClinVar as [Benign]. Clinvar id is 2688151.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=2.12 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITPKBNM_002221.4 linkuse as main transcriptc.1896C>T p.Ala632= synonymous_variant 2/8 ENST00000429204.6
ITPKBNM_001388404.1 linkuse as main transcriptc.1896C>T p.Ala632= synonymous_variant 2/3
ITPKBXM_017001211.3 linkuse as main transcriptc.1896C>T p.Ala632= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPKBENST00000429204.6 linkuse as main transcriptc.1896C>T p.Ala632= synonymous_variant 2/85 NM_002221.4 P1P27987-1
ITPKBENST00000272117.8 linkuse as main transcriptc.1896C>T p.Ala632= synonymous_variant 2/81 P1P27987-1
ITPKBENST00000366784.1 linkuse as main transcriptc.1896C>T p.Ala632= synonymous_variant 2/31 P27987-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.278
AC:
42214
AN:
151946
Hom.:
6038
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.255
Gnomad AMI
AF:
0.382
Gnomad AMR
AF:
0.303
Gnomad ASJ
AF:
0.299
Gnomad EAS
AF:
0.279
Gnomad SAS
AF:
0.297
Gnomad FIN
AF:
0.275
Gnomad MID
AF:
0.291
Gnomad NFE
AF:
0.282
Gnomad OTH
AF:
0.302
GnomAD3 exomes
AF:
0.280
AC:
56973
AN:
203540
Hom.:
8218
AF XY:
0.284
AC XY:
30879
AN XY:
108888
show subpopulations
Gnomad AFR exome
AF:
0.250
Gnomad AMR exome
AF:
0.292
Gnomad ASJ exome
AF:
0.288
Gnomad EAS exome
AF:
0.268
Gnomad SAS exome
AF:
0.292
Gnomad FIN exome
AF:
0.265
Gnomad NFE exome
AF:
0.283
Gnomad OTH exome
AF:
0.297
GnomAD4 exome
AF:
0.280
AC:
391317
AN:
1395582
Hom.:
55557
Cov.:
33
AF XY:
0.281
AC XY:
193469
AN XY:
687692
show subpopulations
Gnomad4 AFR exome
AF:
0.246
Gnomad4 AMR exome
AF:
0.292
Gnomad4 ASJ exome
AF:
0.291
Gnomad4 EAS exome
AF:
0.265
Gnomad4 SAS exome
AF:
0.291
Gnomad4 FIN exome
AF:
0.275
Gnomad4 NFE exome
AF:
0.280
Gnomad4 OTH exome
AF:
0.293
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.278
AC:
42251
AN:
152064
Hom.:
6046
Cov.:
32
AF XY:
0.277
AC XY:
20627
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.255
Gnomad4 AMR
AF:
0.304
Gnomad4 ASJ
AF:
0.299
Gnomad4 EAS
AF:
0.279
Gnomad4 SAS
AF:
0.297
Gnomad4 FIN
AF:
0.275
Gnomad4 NFE
AF:
0.282
Gnomad4 OTH
AF:
0.298
Alfa
AF:
0.280
Hom.:
5145
Bravo
AF:
0.280
Asia WGS
AF:
0.264
AC:
914
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 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
10
Dann
Benign
0.72

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: rs708775; hg19: chr1-226923264; COSMIC: COSV55258723; API