Variant 1-9717528-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005026.5(PIK3CD):c.931-9G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,613,626 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 24 hom., cov: 32)

Exomes 𝑓: 0.023 ( 473 hom. )

Consequence

PIK3CD
NM_005026.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002334

Clinical Significance

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

Conservation

PhyloP100: -0.0980

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:

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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=-0.82).

BP6

Variant 1-9717528-G-C is Benign according to our data. Variant chr1-9717528-G-C is described in ClinVar as [Benign]. Clinvar id is 440067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0169 (2575/152294) while in subpopulation NFE AF= 0.0248 (1686/68018). AF 95% confidence interval is 0.0238. There are 24 homozygotes in gnomad4. There are 1223 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CD	NM_005026.5 linkuse as main transcript	c.931-9G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377346.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CD	ENST00000377346.9 linkuse as main transcript	c.931-9G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005026.5	P3	O00329-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2575

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0170

AC:

4255

AN:

249950

Hom.:

AF XY:

0.0166

AC XY:

2250

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.00469

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0174

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0237

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0227

AC:

33118

AN:

1461332

Hom.:

473

Cov.:

AF XY:

0.0218

AC XY:

15821

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.00353

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.0258

Gnomad4 NFE exome

AF:

0.0262

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0169

AC:

2575

AN:

152294

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1223

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00447

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.0248

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0207

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0229

EpiControl

AF:

0.0231

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

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Immunodeficiency 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.0

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