rs1151804

Positions:

• chr1-226636516-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002221.4(ITPKB):​c.2625+1163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,238 control chromosomes in the GnomAD database, including 825 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (825 hom., cov: 33)
• Consequence: ITPKB NM_002221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKB	NM_002221.4	c.2625+1163G>A		intron_variant		ENST00000429204.6	NP_002212.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKB	ENST00000429204.6	c.2625+1163G>A		intron_variant		5	NM_002221.4	ENSP00000411152	P1
ITPKB	ENST00000272117.8	c.2625+1163G>A		intron_variant		1		ENSP00000272117	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15474 AN: 152120 Hom.: 824 Cov.: 33

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.0771

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0904

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15481 AN: 152238 Hom.: 825 Cov.: 33 AF XY: 0.102 AC XY: 7572 AN XY: 74440

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.0690

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.105 Hom.: 174

Bravo AF: 0.0964

Asia WGS AF: 0.111 AC: 386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs1151804; hg19: chr1-226824217; COSMIC: COSV55269494;