Variant chr1-9716517-A-G 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.678A>G(p.Thr226Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,610,348 control chromosomes in the GnomAD database, including 574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 233 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 341 hom. )

Consequence

PIK3CD
NM_005026.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.09

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-9716517-A-G is Benign according to our data. Variant chr1-9716517-A-G is described in ClinVar as [Benign]. Clinvar id is 474033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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.678A>G	p.Thr226Thr	synonymous_variant	6/24	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.678A>G	p.Thr226Thr	synonymous_variant	6/24	1	NM_005026.5	ENSP00000366563.4		O00329-1

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

5577

AN:

152170

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0197

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0429

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0412

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0182

AC:

4479

AN:

246058

Hom.:

121

AF XY:

0.0151

AC XY:

2020

AN XY:

134148

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.0200

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.0419

Gnomad SAS exome

AF:

0.00497

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.00753

AC:

10982

AN:

1458060

Hom.:

341

Cov.:

AF XY:

0.00710

AC XY:

5148

AN XY:

725350

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0198

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0513

Gnomad4 SAS exome

AF:

0.00453

Gnomad4 FIN exome

AF:

0.0373

Gnomad4 NFE exome

AF:

0.000979

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0367

AC:

5596

AN:

152288

Hom.:

233

Cov.:

AF XY:

0.0381

AC XY:

2835

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0430

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0412

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0400

Asia WGS

AF:

0.0290

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.11

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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