Variant 22-20710068-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_058004.4(PI4KA):c.6084-71T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 834,838 control chromosomes in the GnomAD database, including 82,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16958 hom., cov: 33)

Exomes 𝑓: 0.43 ( 65604 hom. )

Consequence

PI4KA
NM_058004.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 22-20710068-A-C is Benign according to our data. Variant chr22-20710068-A-C is described in ClinVar as [Benign]. Clinvar id is 1275198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4KA	NM_058004.4 linkuse as main transcript	c.6084-71T>G		intron_variant		ENST00000255882.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4KA	ENST00000255882.11 linkuse as main transcript	c.6084-71T>G		intron_variant		1	NM_058004.4	P1	P42356-1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71113

AN:

151578

Hom.:

16938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.434

AC:

296647

AN:

683140

Hom.:

65604

Cov.:

AF XY:

0.432

AC XY:

158421

AN XY:

366978

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.571

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.522

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.430

Gnomad4 OTH exome

AF:

0.447

GnomAD4 genome

AF:

0.469

AC:

71179

AN:

151698

Hom.:

16958

Cov.:

AF XY:

0.463

AC XY:

34322

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.527

Gnomad4 AMR

AF:

0.529

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.527

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.461

Hom.:

1974

Bravo

AF:

0.494

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.55

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over