chr1-9686190-A-G

Position:

• chr1-9686190-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377346.9(PIK3CD):​c.-137-5277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,964 control chromosomes in the GnomAD database, including 1,939 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 0.14 (1939 hom., cov: 31)
• Consequence: PIK3CD ENST00000377346.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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-AS2 (HGNC:51334): (PIK3CD antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CD	NM_005026.5	c.-137-5277A>G		intron_variant		ENST00000377346.9	NP_005017.3
PIK3CD-AS2	NR_126367.1	n.240+1145T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9	c.-137-5277A>G		intron_variant		1	NM_005026.5	ENSP00000366563	P3
PIK3CD-AS2	ENST00000415330.4	n.249+1145T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21653 AN: 151848 Hom.: 1924 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.143 AC: 21710 AN: 151964 Hom.: 1939 Cov.: 31 AF XY: 0.146 AC XY: 10864 AN XY: 74268

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.141

Alfa AF: 0.101 Hom.: 1314

Bravo AF: 0.154

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.63

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: rs6677649; hg19: chr1-9746248;