3-138666573-C-T

Variant names:

• chr3-138666573-C-T
• rs9878820
• NM_006219.3:c.2505-1370G>A

Variant summary

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

The NM_006219.3(PIK3CB):​c.2505-1370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,012 control chromosomes in the GnomAD database, including 12,252 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 0.36 (12252 hom., cov: 32)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	NM_006219.3	MANE Select	c.2505-1370G>A		intron	N/A	NP_006210.1
	PIK3CB	NM_001437286.1		c.2505-1370G>A		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.2505-1370G>A		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.2505-1370G>A		intron	N/A	ENSP00000501150.1
	PIK3CB	ENST00000289153.6	TSL:1	c.2505-1370G>A		intron	N/A	ENSP00000289153.2
	PIK3CB	ENST00000544716.5	TSL:1	c.858-1370G>A		intron	N/A	ENSP00000438259.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54541 AN: 151894 Hom.: 12240 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.359 AC: 54566 AN: 152012 Hom.: 12252 Cov.: 32 AF XY: 0.365 AC XY: 27113 AN XY: 74290

African (AFR) AF: 0.0860 AC: 3565 AN: 41468

American (AMR) AF: 0.541 AC: 8263 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2327 AN: 5164

South Asian (SAS) AF: 0.443 AC: 2142 AN: 4832

European-Finnish (FIN) AF: 0.472 AC: 4965 AN: 10530

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30791 AN: 67952

Other (OTH) AF: 0.372 AC: 787 AN: 2114

Alfa AF: 0.409 Hom.: 10027

Bravo AF: 0.355

Asia WGS AF: 0.450 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.43
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9878820; hg19: chr3-138385415;