Variant rs140468930 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005026.5(PIK3CD):c.1953C>T(p.Leu651Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 1,612,992 control chromosomes in the GnomAD database, including 806 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 65 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 741 hom. )

Consequence

PIK3CD
NM_005026.5 splice_region, synonymous

Scores

Splicing: ADA: 0.006946

Clinical Significance

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

Conservation

PhyloP100: 0.974

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 (HGNC:):

PIK3CD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-9721585-C-T is Benign according to our data. Variant chr1-9721585-C-T is described in ClinVar as [Benign]. Clinvar id is 474025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.974 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CD	NM_005026.5 linkuse as main transcript	c.1953C>T	p.Leu651Leu	splice_region_variant, synonymous_variant	15/24	ENST00000377346.9	NP_005017.3	O00329-1A0A2K8FKV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9 linkuse as main transcript	c.1953C>T	p.Leu651Leu	splice_region_variant, synonymous_variant	15/24	1	NM_005026.5	ENSP00000366563.4		O00329-1

Frequencies

GnomAD3 genomes

AF:

0.00981

AC:

1493

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00750

Gnomad SAS

AF:

0.0446

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.0295

AC:

7343

AN:

249322

Hom.:

546

AF XY:

0.0254

AC XY:

3433

AN XY:

135036

show subpopulations

Gnomad AFR exome

AF:

0.000995

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00902

Gnomad SAS exome

AF:

0.0454

Gnomad FIN exome

AF:

0.00604

Gnomad NFE exome

AF:

0.000676

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.00826

AC:

12065

AN:

1460658

Hom.:

741

Cov.:

AF XY:

0.00847

AC XY:

6157

AN XY:

726604

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.0425

Gnomad4 FIN exome

AF:

0.00639

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.00791

GnomAD4 genome

AF:

0.00983

AC:

1498

AN:

152334

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

854

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.0697

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00752

Gnomad4 SAS

AF:

0.0445

Gnomad4 FIN

AF:

0.00546

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

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	Jun 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Immunodeficiency 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0069

dbscSNV1_RF

Benign

0.42

SpliceAI score (max)

0.030

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