3-138681490-C-T

Position:

• chr3-138681490-C-T

Variant summary

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

The NM_006219.3(PIK3CB):​c.2504+477G>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 151,840 control chromosomes in the GnomAD database, including 12,234 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 (12234 hom., cov: 32)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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]

PIK3CB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CB	NM_006219.3	c.2504+477G>A		intron_variant		ENST00000674063.1	NP_006210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CB	ENST00000674063.1	c.2504+477G>A		intron_variant			NM_006219.3	ENSP00000501150.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54496 AN: 151720 Hom.: 12222 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.350

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: 54521 AN: 151840 Hom.: 12234 Cov.: 32 AF XY: 0.365 AC XY: 27078 AN XY: 74194

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.373

Alfa AF: 0.432 Hom.: 23497

Bravo AF: 0.355

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.81

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: rs12493155; hg19: chr3-138400332;