rs500687

Positions:

• chr3-138741361-G-A
• chr3-138741361-G-C
• chr3-138741361-G-T

Variant summary

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

The NM_006219.3(PIK3CB):​c.621+1197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,066 control chromosomes in the GnomAD database, including 26,681 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 (26681 hom., cov: 32)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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=-1.02).
• 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	Protein	UniProt
PIK3CB	NM_006219.3	c.621+1197C>T		intron_variant		ENST00000674063.1	NP_006210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CB	ENST00000674063.1	c.621+1197C>T		intron_variant			NM_006219.3	ENSP00000501150.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88620 AN: 151948 Hom.: 26642 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.583 AC: 88718 AN: 152066 Hom.: 26681 Cov.: 32 AF XY: 0.595 AC XY: 44235 AN XY: 74344

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.559

Alfa AF: 0.540 Hom.: 43025

Bravo AF: 0.583

Asia WGS AF: 0.816 AC: 2835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs500687; hg19: chr3-138460203;