rs113176101

chr1-9715846-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005026.5(PIK3CD):c.371-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,611,486 control chromosomes in the GnomAD database, including 156 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 0.017 (74 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (82 hom.)
• Consequence: PIK3CD NM_005026.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001669
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-9715846-C-T is Benign according to our data. Variant chr1-9715846-C-T is described in ClinVar as [Benign]. Clinvar id is 474030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CD	NM_005026.5	c.371-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377346.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CD	ENST00000377346.9	c.371-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005026.5	P3

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2504 AN: 152218 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00817

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00412 AC: 995 AN: 241436 Hom.: 22 AF XY: 0.00297 AC XY: 393 AN XY: 132306

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000276

Gnomad SAS exome AF: 0.000755

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000206

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00180 AC: 2633 AN: 1459150 Hom.: 82 Cov.: 42 AF XY: 0.00163 AC XY: 1183 AN XY: 725884

Gnomad4 AFR exome AF: 0.0598

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.000743

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000954

Gnomad4 OTH exome AF: 0.00449

GnomAD4 genome AF: 0.0166 AC: 2536 AN: 152336 Hom.: 74 Cov.: 33 AF XY: 0.0166 AC XY: 1235 AN XY: 74498

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00686 Hom.: 10

Bravo AF: 0.0193

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 16, 2023

- -

Immunodeficiency 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	12
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.23
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

Other links and lift over

dbSNP: rs113176101; hg19: chr1-9775904;