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GeneBe

1-226735683-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002221.4(ITPKB):c.1776C>T(p.Asn592=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,605,932 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 15 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 104 hom. )

Consequence

ITPKB
NM_002221.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66
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 -15 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=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-226735683-G-A is Benign according to our data. Variant chr1-226735683-G-A is described in ClinVar as [Benign]. Clinvar id is 777333.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=1.66 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 = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITPKBNM_002221.4 linkuse as main transcriptc.1776C>T p.Asn592= synonymous_variant 2/8 ENST00000429204.6
ITPKBNM_001388404.1 linkuse as main transcriptc.1776C>T p.Asn592= synonymous_variant 2/3
ITPKBXM_017001211.3 linkuse as main transcriptc.1776C>T p.Asn592= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITPKBENST00000429204.6 linkuse as main transcriptc.1776C>T p.Asn592= synonymous_variant 2/85 NM_002221.4 P1P27987-1
ITPKBENST00000272117.8 linkuse as main transcriptc.1776C>T p.Asn592= synonymous_variant 2/81 P1P27987-1
ITPKBENST00000366784.1 linkuse as main transcriptc.1776C>T p.Asn592= synonymous_variant 2/31 P27987-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00420
AC:
639
AN:
152126
Hom.:
15
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0156
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0563
Gnomad SAS
AF:
0.0101
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00936
AC:
2285
AN:
244170
Hom.:
45
AF XY:
0.00854
AC XY:
1129
AN XY:
132132
show subpopulations
Gnomad AFR exome
AF:
0.000248
Gnomad AMR exome
AF:
0.0253
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0590
Gnomad SAS exome
AF:
0.00958
Gnomad FIN exome
AF:
0.00108
Gnomad NFE exome
AF:
0.000335
Gnomad OTH exome
AF:
0.00509
GnomAD4 exome
AF:
0.00317
AC:
4606
AN:
1453688
Hom.:
104
Cov.:
34
AF XY:
0.00327
AC XY:
2365
AN XY:
722484
show subpopulations
Gnomad4 AFR exome
AF:
0.000362
Gnomad4 AMR exome
AF:
0.0261
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0504
Gnomad4 SAS exome
AF:
0.00940
Gnomad4 FIN exome
AF:
0.00126
Gnomad4 NFE exome
AF:
0.000309
Gnomad4 OTH exome
AF:
0.00417
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00420
AC:
640
AN:
152244
Hom.:
15
Cov.:
32
AF XY:
0.00455
AC XY:
339
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.0156
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0564
Gnomad4 SAS
AF:
0.0106
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00102
Hom.:
1
Bravo
AF:
0.00545
Asia WGS
AF:
0.0170
AC:
58
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
3.7
Dann
Benign
0.47

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: rs55822534; hg19: chr1-226923384; API