NM_002221.4:c.2625+1163G>A

Variant names:

• chr1-226636516-C-T
• rs1151804
• NM_002221.4:c.2625+1163G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ITPKB Gene-Disease associations (from GenCC):

• ITPKB deficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ITPKB	NM_002221.4	c.2625+1163G>A		intron_variant	Intron 7 of 7	ENST00000429204.6	NP_002212.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPKB	ENST00000429204.6	c.2625+1163G>A		intron_variant	Intron 7 of 7	5	NM_002221.4	ENSP00000411152.1
ITPKB	ENST00000272117.8	c.2625+1163G>A		intron_variant	Intron 7 of 7	1		ENSP00000272117.3

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

African (AFR) AF: 0.0931 AC: 3869 AN: 41546

American (AMR) AF: 0.0690 AC: 1056 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3468

East Asian (EAS) AF: 0.155 AC: 804 AN: 5174

South Asian (SAS) AF: 0.127 AC: 611 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7230 AN: 67998

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

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
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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