rs2251844

Positions:

• chr15-43544280-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K1	NM_001394395.1	c.3557-4697A>G		intron_variant		ENST00000420765.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K1	ENST00000420765.6	c.3557-4697A>G		intron_variant		5	NM_001394395.1	A2

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

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.237

Alfa AF: 0.136 Hom.: 3010

Bravo AF: 0.302

Asia WGS AF: 0.351 AC: 1218 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.79

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: rs2251844; hg19: chr15-43836478;