ENST00000462560.6:n.547+763A>G

Variant names:

• chr22-21486037-T-C
• rs399557
• ENST00000462560.6:n.547+763A>G

Variant summary

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

The ENST00000462560.6(ENSG00000293427):​n.547+763A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 149,030 control chromosomes in the GnomAD database, including 54,319 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 0.84 (54319 hom., cov: 29)
• Consequence: ENSG00000293427 ENST00000462560.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 3 publications found

Genes affected

ENSG00000293427 (HGNC:):

PI4KAP2 (HGNC:33577): (phosphatidylinositol 4-kinase alpha pseudogene 2) Predicted to enable 1-phosphatidylinositol 4-kinase activity. Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and phosphatidylinositol-mediated signaling. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4KAP2	NR_003700.1	n.814+763A>G		intron_variant	Intron 6 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293427	ENST00000462560.6	n.547+763A>G		intron_variant	Intron 4 of 14	1
ENSG00000293427	ENST00000479693.1	n.843+763A>G		intron_variant	Intron 6 of 12	1
PI4KAP2	ENST00000360806.9	n.523+763A>G		intron_variant	Intron 4 of 15	6

Frequencies

GnomAD3 genomes AF: 0.843 AC: 125582 AN: 148916 Hom.: 54277 Cov.: 29

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.858

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.843 AC: 125675 AN: 149030 Hom.: 54319 Cov.: 29 AF XY: 0.832 AC XY: 60448 AN XY: 72670

African (AFR) AF: 0.859 AC: 35390 AN: 41180

American (AMR) AF: 0.712 AC: 10659 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3020 AN: 3452

East Asian (EAS) AF: 0.501 AC: 2550 AN: 5086

South Asian (SAS) AF: 0.570 AC: 2656 AN: 4660

European-Finnish (FIN) AF: 0.870 AC: 8709 AN: 10016

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 59950 AN: 66398

Other (OTH) AF: 0.831 AC: 1721 AN: 2072

Alfa AF: 0.878 Hom.: 5990

Bravo AF: 0.831

Asia WGS AF: 0.538 AC: 1870 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.014
DANN	Benign	0.080
PhyloP100		-2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs399557; hg19: chr22-21840326;