rs165789

chr22-20817304-G-A

Variant summary

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

The NM_058004.4(PI4KA):c.856+1179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,874 control chromosomes in the GnomAD database, including 18,575 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 0.49 (18575 hom., cov: 31)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

Genes affected

PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4	c.856+1179C>T		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11	c.856+1179C>T		intron_variant		1	NM_058004.4	P1
PI4KA	ENST00000485963.5	n.943+1179C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74013 AN: 151756 Hom.: 18555 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.488 AC: 74084 AN: 151874 Hom.: 18575 Cov.: 31 AF XY: 0.481 AC XY: 35733 AN XY: 74224

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.513

Alfa AF: 0.471 Hom.: 2114

Bravo AF: 0.512

Asia WGS AF: 0.477 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.35
Dann	Benign	0.48

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: rs165789; hg19: chr22-21171592;