rs9879784

Variant names:

• chr3-138814661-G-C
• rs9879784
• NM_006219.3:c.-121-18094C>G

Variant summary

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

The NM_006219.3(PIK3CB):​c.-121-18094C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,584 control chromosomes in the GnomAD database, including 10,630 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 0.35 (10630 hom., cov: 30)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 1 publications found

Genes affected

PIK3CB (HGNC:8976): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) This gene encodes an isoform of the catalytic subunit of phosphoinositide 3-kinase (PI3K). These kinases are important in signaling pathways involving receptors on the outer membrane of eukaryotic cells and are named for their catalytic subunit. The encoded protein is the catalytic subunit for PI3Kbeta (PI3KB). PI3KB has been shown to be part of the activation pathway in neutrophils which have bound immune complexes at sites of injury or infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006219.3. 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
	PIK3CB	NM_006219.3	MANE Select	c.-121-18094C>G		intron	N/A	NP_006210.1	P42338
	PIK3CB	NM_001437286.1		c.-17+20034C>G		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.-188-18094C>G		intron	N/A	NP_001424216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.-121-18094C>G		intron	N/A	ENSP00000501150.1	P42338
	PIK3CB	ENST00000477593.6	TSL:5	c.-17+20034C>G		intron	N/A	ENSP00000418143.1	P42338
	PIK3CB	ENST00000894539.1		c.-219-18094C>G		intron	N/A	ENSP00000564598.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52709 AN: 151468 Hom.: 10632 Cov.: 30

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.0155

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.348 AC: 52705 AN: 151584 Hom.: 10630 Cov.: 30 AF XY: 0.338 AC XY: 25034 AN XY: 74022

African (AFR) AF: 0.193 AC: 7987 AN: 41326

American (AMR) AF: 0.310 AC: 4701 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3466

East Asian (EAS) AF: 0.0154 AC: 79 AN: 5146

South Asian (SAS) AF: 0.340 AC: 1629 AN: 4790

European-Finnish (FIN) AF: 0.338 AC: 3528 AN: 10446

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31556 AN: 67924

Other (OTH) AF: 0.382 AC: 802 AN: 2102

Alfa AF: 0.387 Hom.: 1561

Bravo AF: 0.337

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		0.084
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9879784; hg19: chr3-138533503;