rs178051

Positions:

• chr22-20818210-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_058004.4(PI4KA):​c.856+273A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,240 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (397 hom., cov: 32)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.626

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]

PI4KA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-20818210-T-C is Benign according to our data. Variant chr22-20818210-T-C is described in ClinVar as [Benign]. Clinvar id is 1271540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI4KA	NM_058004.4	c.856+273A>G		intron_variant		ENST00000255882.11	NP_477352.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI4KA	ENST00000255882.11	c.856+273A>G		intron_variant		1	NM_058004.4	ENSP00000255882.6
PI4KA	ENST00000485963.5	n.943+273A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8916 AN: 152122 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.0841

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

GnomAD4 genome AF: 0.0585 AC: 8912 AN: 152240 Hom.: 397 Cov.: 32 AF XY: 0.0566 AC XY: 4215 AN XY: 74438

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0660

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.0488

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0742 Hom.: 262

Bravo AF: 0.0595

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.75
DANN	Benign	0.51

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: rs178051; hg19: chr22-21172498;