rs10916025

Positions:

• chr1-226668188-G-C
• chr1-226668188-G-T

Variant summary

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

The NM_002221.4(ITPKB):​c.1933-19417C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,152 control chromosomes in the GnomAD database, including 1,947 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 0.14 (1947 hom., cov: 32)
• Consequence: ITPKB NM_002221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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]

LOC124904529 (HGNC:):

ITPKB-IT1 (HGNC:41349): (ITPKB intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKB	NM_002221.4	c.1933-19417C>G		intron_variant		ENST00000429204.6	NP_002212.3
LOC124904529	XR_007066908.1	n.3898G>C		non_coding_transcript_exon_variant	2/2
ITPKB-IT1	NR_103784.1	n.152+6729C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKB	ENST00000429204.6	c.1933-19417C>G		intron_variant		5	NM_002221.4	ENSP00000411152	P1
ITPKB	ENST00000272117.8	c.1933-19417C>G		intron_variant		1		ENSP00000272117	P1
ITPKB-IT1	ENST00000412918.3	n.176+6729C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21693 AN: 152034 Hom.: 1941 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.143 AC: 21717 AN: 152152 Hom.: 1947 Cov.: 32 AF XY: 0.140 AC XY: 10439 AN XY: 74376

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.160

Alfa AF: 0.152 Hom.: 239

Bravo AF: 0.145

Asia WGS AF: 0.201 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
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: rs10916025; hg19: chr1-226855889; COSMIC: COSV55259039; COSMIC: COSV55259039;