1-9690399-T-C

Variant names:

• chr1-9690399-T-C
• rs4240910
• NM_005026.5:c.-137-1068T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005026.5(PIK3CD):​c.-137-1068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,134 control chromosomes in the GnomAD database, including 17,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17750 hom., cov: 32)
• Consequence: PIK3CD NM_005026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• immunodeficiency 14b, autosomal recessive

  Inheritance: AR, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• activated PI3K-delta syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CD	NM_005026.5	c.-137-1068T>C		intron_variant	Intron 1 of 23	ENST00000377346.9	NP_005017.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9	c.-137-1068T>C		intron_variant	Intron 1 of 23	1	NM_005026.5	ENSP00000366563.4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73526 AN: 152016 Hom.: 17734 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.484 AC: 73584 AN: 152134 Hom.: 17750 Cov.: 32 AF XY: 0.487 AC XY: 36190 AN XY: 74366

African (AFR) AF: 0.478 AC: 19824 AN: 41504

American (AMR) AF: 0.528 AC: 8064 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1664 AN: 3466

East Asian (EAS) AF: 0.459 AC: 2372 AN: 5164

South Asian (SAS) AF: 0.604 AC: 2915 AN: 4828

European-Finnish (FIN) AF: 0.465 AC: 4920 AN: 10580

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32301 AN: 67996

Other (OTH) AF: 0.482 AC: 1017 AN: 2110

Alfa AF: 0.492 Hom.: 12438

Bravo AF: 0.487

Asia WGS AF: 0.525 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.27
DANN	Benign	0.79
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4240910; hg19: chr1-9750457;