rs2881900

Variant names:

• chr3-138830167-A-G
• rs2881900
• NM_006219.3:c.-122+4528T>C

Variant summary

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

The ENST00000674063.1(PIK3CB):​c.-122+4528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,904 control chromosomes in the GnomAD database, including 22,236 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 0.51 (22236 hom., cov: 31)
• Consequence: PIK3CB ENST00000674063.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674063.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	NM_006219.3	MANE Select	c.-122+4528T>C		intron	N/A	NP_006210.1
	PIK3CB	NM_001437286.1		c.-17+4528T>C		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.-189+4528T>C		intron	N/A	NP_001424216.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.-122+4528T>C		intron	N/A	ENSP00000501150.1
	PIK3CB	ENST00000477593.6	TSL:5	c.-17+4528T>C		intron	N/A	ENSP00000418143.1
	PIK3CB	ENST00000483968.5	TSL:3	c.-189+4528T>C		intron	N/A	ENSP00000419857.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77333 AN: 151786 Hom.: 22203 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.510 AC: 77412 AN: 151904 Hom.: 22236 Cov.: 31 AF XY: 0.494 AC XY: 36680 AN XY: 74248

African (AFR) AF: 0.746 AC: 30912 AN: 41414

American (AMR) AF: 0.387 AC: 5902 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1839 AN: 3464

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5172

South Asian (SAS) AF: 0.343 AC: 1650 AN: 4806

European-Finnish (FIN) AF: 0.336 AC: 3548 AN: 10556

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31773 AN: 67948

Other (OTH) AF: 0.504 AC: 1061 AN: 2106

Alfa AF: 0.487 Hom.: 2423

Bravo AF: 0.522

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.85
DANN	Benign	0.69
PhyloP100		-1.1
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: rs2881900; hg19: chr3-138549009;