3-138707586-T-C

Position:

• chr3-138707586-T-C

Variant summary

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

The NM_006219.3(PIK3CB):​c.1400-297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,103,350 control chromosomes in the GnomAD database, including 166,085 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 0.58 (26124 hom., cov: 32)
  • Exomes 𝑓: 0.54 (139961 hom.)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CB	NM_006219.3	c.1400-297A>G		intron_variant		ENST00000674063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CB	ENST00000674063.1	c.1400-297A>G		intron_variant			NM_006219.3	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87666 AN: 151996 Hom.: 26089 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.539 AC: 512304 AN: 951236 Hom.: 139961 Cov.: 16 AF XY: 0.539 AC XY: 241229 AN XY: 447808

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.577 AC: 87757 AN: 152114 Hom.: 26124 Cov.: 32 AF XY: 0.589 AC XY: 43773 AN XY: 74370

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.556

Alfa AF: 0.565 Hom.: 3165

Bravo AF: 0.575

Asia WGS AF: 0.815 AC: 2831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.42

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: rs361084; hg19: chr3-138426428;