Variant chr1-9654282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005026.5(PIK3CD):c.-138+2480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00838 in 1,367,744 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 58 hom. )

Consequence

PIK3CD
NM_005026.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.106

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-9654282-C-T is Benign according to our data. Variant chr1-9654282-C-T is described in ClinVar as [Benign]. Clinvar id is 2638188.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00652 (993/152350) while in subpopulation AMR AF= 0.00994 (152/15296). AF 95% confidence interval is 0.00932. There are 8 homozygotes in gnomad4. There are 462 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CD	NM_005026.5 linkuse as main transcript	c.-138+2480C>T		intron_variant		ENST00000377346.9
PIK3CD-AS1	NR_027045.1 linkuse as main transcript	n.305G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CD	ENST00000377346.9 linkuse as main transcript	c.-138+2480C>T		intron_variant		1	NM_005026.5	P3	O00329-1
PIK3CD-AS1	ENST00000377320.3 linkuse as main transcript	n.305G>A		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

994

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00995

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00617

AC:

1539

AN:

249260

Hom.:

AF XY:

0.00612

AC XY:

827

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00707

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00871

Gnomad OTH exome

AF:

0.00909

GnomAD4 exome

AF:

0.00861

AC:

10470

AN:

1215394

Hom.:

Cov.:

AF XY:

0.00836

AC XY:

5034

AN XY:

602330

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00762

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.00117

Gnomad4 NFE exome

AF:

0.00961

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00652

AC:

993

AN:

152350

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00994

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00927

Hom.:

Bravo

AF:

0.00714

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

PIK3CD: BS1, BS2; PIK3CD-AS1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.6

DANN

Benign

0.75

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