rs4727666

Variant names:

• chr7-106865033-G-A
• rs4727666
• NM_001282426.2:c.-406G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-106865033-G-A
• chr7-106865033-G-C
• chr7-106865033-G-T

Variant summary

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

The NM_001282426.2(PIK3CG):​c.-406G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,948 control chromosomes in the GnomAD database, including 41,947 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 0.73 (41947 hom., cov: 31)
• Consequence: PIK3CG NM_001282426.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 10 publications found

Genes affected

PIK3CG (HGNC:8978): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I catalytic subunit of PI3K. Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K. This gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2015]

PIK3CG Gene-Disease associations (from GenCC):

• immunodeficiency 97 with autoinflammation

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CG	NM_001282426.2	MANE Select	c.-406G>A		upstream_gene	N/A	NP_001269355.1	P48736
	PIK3CG	NM_001282427.2		c.-330G>A		upstream_gene	N/A	NP_001269356.1	P48736

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CG	ENST00000496166.6	TSL:1 MANE Select	c.-406G>A		upstream_gene	N/A	ENSP00000419260.1	P48736
	PIK3CG	ENST00000440650.6	TSL:1	c.-330G>A		upstream_gene	N/A	ENSP00000392258.2	P48736

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111369 AN: 151828 Hom.: 41926 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.733 AC: 111431 AN: 151948 Hom.: 41947 Cov.: 31 AF XY: 0.740 AC XY: 54953 AN XY: 74292

African (AFR) AF: 0.548 AC: 22649 AN: 41334

American (AMR) AF: 0.778 AC: 11875 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2517 AN: 3468

East Asian (EAS) AF: 0.935 AC: 4838 AN: 5176

South Asian (SAS) AF: 0.809 AC: 3897 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8886 AN: 10574

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54294 AN: 67988

Other (OTH) AF: 0.743 AC: 1567 AN: 2110

Alfa AF: 0.774 Hom.: 74912

Bravo AF: 0.717

Asia WGS AF: 0.853 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		-1.1
PromoterAI		0.028	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4727666; hg19: chr7-106505478; COSMIC: COSV63249430;