Variant 1-9654307-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_005026.5(PIK3CD):c.-138+2505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,367,746 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 23 hom. )

Consequence

PIK3CD
NM_005026.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.701

Variant links:

Genes affected

PIK3CD (HGNC:8977): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]

PIK3CD links:

PIK3CD-AS1 (HGNC:32346): (PIK3CD antisense RNA 1)

PIK3CD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-9654307-G-A is Benign according to our data. Variant chr1-9654307-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638189.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0047 (716/152342) while in subpopulation AFR AF= 0.00844 (351/41574). AF 95% confidence interval is 0.00771. There are 1 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 23 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CD	NM_005026.5 linkuse as main transcript	c.-138+2505G>A		intron_variant		ENST00000377346.9	NP_005017.3
PIK3CD-AS1	NR_027045.1 linkuse as main transcript	n.280C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9 linkuse as main transcript	c.-138+2505G>A		intron_variant		1	NM_005026.5	ENSP00000366563	P3	O00329-1
PIK3CD-AS1	ENST00000377320.3 linkuse as main transcript	n.280C>T		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

708

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00372

AC:

927

AN:

249270

Hom.:

AF XY:

0.00404

AC XY:

546

AN XY:

135230

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00689

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00287

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00300

AC:

3647

AN:

1215404

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

1998

AN XY:

602338

show subpopulations

Gnomad4 AFR exome

AF:

0.00966

Gnomad4 AMR exome

AF:

0.00290

Gnomad4 ASJ exome

AF:

0.00941

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00685

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00536

GnomAD4 genome

AF:

0.00470

AC:

716

AN:

152342

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

335

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00844

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.00524

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00367

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

PIK3CD-AS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.1

DANN

Uncertain

0.98

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