1-9690399-T-C

Position:

• chr1-9690399-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
PIK3CD	NM_005026.5	c.-137-1068T>C		intron_variant		ENST00000377346.9	NP_005017.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9	c.-137-1068T>C		intron_variant		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

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.482

Alfa AF: 0.494 Hom.: 9373

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4240910; hg19: chr1-9750457;