rs4748812

Variant names:

• chr10-22550154-G-A
• rs4748812
• NM_005028.5:c.792+505C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005028.5(PIP4K2A):​c.792+505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,942 control chromosomes in the GnomAD database, including 24,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (24546 hom., cov: 32)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217
• Publications: 6 publications found

Genes affected

PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-22550154-G-A is Benign according to our data. Variant chr10-22550154-G-A is described in ClinVar as [Benign]. Clinvar id is 1291277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.792+505C>T		intron_variant	Intron 7 of 9	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.792+505C>T		intron_variant	Intron 7 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.615+505C>T		intron_variant	Intron 7 of 9	2		ENSP00000442098.1
PIP4K2A	ENST00000323883.11	c.372+505C>T		intron_variant	Intron 5 of 7	2		ENSP00000326294.7
PIP4K2A	ENST00000604912.1	c.330+505C>T		intron_variant	Intron 4 of 4	2		ENSP00000473858.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84112 AN: 151824 Hom.: 24536 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.554 AC: 84139 AN: 151942 Hom.: 24546 Cov.: 32 AF XY: 0.564 AC XY: 41902 AN XY: 74278

African (AFR) AF: 0.355 AC: 14687 AN: 41390

American (AMR) AF: 0.706 AC: 10799 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1811 AN: 3462

East Asian (EAS) AF: 0.587 AC: 3033 AN: 5170

South Asian (SAS) AF: 0.743 AC: 3575 AN: 4812

European-Finnish (FIN) AF: 0.635 AC: 6706 AN: 10556

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41716 AN: 67948

Other (OTH) AF: 0.588 AC: 1241 AN: 2112

Alfa AF: 0.581 Hom.: 3267

Bravo AF: 0.543

Asia WGS AF: 0.643 AC: 2235 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29923177) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-0.22
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: rs4748812; hg19: chr10-22839083;