rs2251844

Variant names:

• chr15-43544280-T-C
• rs2251844
• NM_001394395.1:c.3557-4697A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394395.1(PPIP5K1):​c.3557-4697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,104 control chromosomes in the GnomAD database, including 9,600 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 0.27 (9600 hom., cov: 31)
• Consequence: PPIP5K1 NM_001394395.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.404
• Publications: 28 publications found

Genes affected

PPIP5K1 (HGNC:29023): (diphosphoinositol pentakisphosphate kinase 1) This gene encodes a dual functional inositol kinase. The encoded enzyme converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate and diphosphoinositol pentakisphosphate to bis-diphosphoinositol tetrakisphosphate. This protein may be important for intracellular signaling pathways. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 15.[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394395.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K1	NM_001394395.1	MANE Select	c.3557-4697A>G		intron	N/A	NP_001381324.1
	PPIP5K1	NM_001393969.1		c.3461-4697A>G		intron	N/A	NP_001380898.1
	PPIP5K1	NM_001393970.1		c.3461-4697A>G		intron	N/A	NP_001380899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K1	ENST00000420765.6	TSL:5 MANE Select	c.3557-4697A>G		intron	N/A	ENSP00000400887.2
	PPIP5K1	ENST00000396923.7	TSL:1	c.3386-4697A>G		intron	N/A	ENSP00000380129.2
	PPIP5K1	ENST00000334933.8	TSL:1	c.3311-4697A>G		intron	N/A	ENSP00000334779.4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41247 AN: 151986 Hom.: 9578 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.272 AC: 41318 AN: 152104 Hom.: 9600 Cov.: 31 AF XY: 0.268 AC XY: 19943 AN XY: 74368

African (AFR) AF: 0.625 AC: 25890 AN: 41440

American (AMR) AF: 0.213 AC: 3254 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2231 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1093 AN: 4818

European-Finnish (FIN) AF: 0.0803 AC: 852 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0983 AC: 6687 AN: 68014

Other (OTH) AF: 0.237 AC: 500 AN: 2108

Alfa AF: 0.159 Hom.: 10306

Bravo AF: 0.302

Asia WGS AF: 0.351 AC: 1218 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.79
PhyloP100		0.40
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: rs2251844; hg19: chr15-43836478;