rs1400266

Positions:

• chr3-138803794-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.-121-7227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,908 control chromosomes in the GnomAD database, including 10,425 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 0.34 (10425 hom., cov: 31)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CB	NM_006219.3	c.-121-7227A>G		intron_variant		ENST00000674063.1	NP_006210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CB	ENST00000674063.1	c.-121-7227A>G		intron_variant			NM_006219.3	ENSP00000501150	P1
PIK3CB	ENST00000477593.5	c.-17+30901A>G		intron_variant		5		ENSP00000418143	P1
PIK3CB	ENST00000483968.5	c.-188-7227A>G		intron_variant		3		ENSP00000419857
PIK3CB	ENST00000462898.5	c.-17+30901A>G		intron_variant, NMD_transcript_variant		5		ENSP00000420108

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51723 AN: 151788 Hom.: 10427 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.340 AC: 51713 AN: 151908 Hom.: 10425 Cov.: 31 AF XY: 0.331 AC XY: 24581 AN XY: 74248

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.376

Alfa AF: 0.389 Hom.: 4891

Bravo AF: 0.329

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1400266; hg19: chr3-138522636;