chr3-138759702-G-A

Variant names:

• chr3-138759702-G-A
• rs361072
• NM_006219.3:c.-16-343C>T

Variant summary

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

The NM_006219.3(PIK3CB):​c.-16-343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,896 control chromosomes in the GnomAD database, including 28,395 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 0.60 (28395 hom., cov: 32)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 24 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=-0.94).
• 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 rank	MANE	Protein	UniProt
PIK3CB	NM_006219.3	c.-16-343C>T		intron_variant	Intron 2 of 23	ENST00000674063.1	NP_006210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CB	ENST00000674063.1	c.-16-343C>T		intron_variant	Intron 2 of 23		NM_006219.3	ENSP00000501150.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91369 AN: 151778 Hom.: 28350 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.602 AC: 91471 AN: 151896 Hom.: 28395 Cov.: 32 AF XY: 0.613 AC XY: 45503 AN XY: 74230

African (AFR) AF: 0.635 AC: 26334 AN: 41454

American (AMR) AF: 0.667 AC: 10169 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1670 AN: 3468

East Asian (EAS) AF: 0.985 AC: 5091 AN: 5170

South Asian (SAS) AF: 0.658 AC: 3169 AN: 4818

European-Finnish (FIN) AF: 0.658 AC: 6910 AN: 10502

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.535 AC: 36338 AN: 67922

Other (OTH) AF: 0.578 AC: 1221 AN: 2112

Alfa AF: 0.561 Hom.: 66598

Bravo AF: 0.606

Asia WGS AF: 0.819 AC: 2846 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.45
PhyloP100		-1.1
PromoterAI		-0.0038	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs361072; hg19: chr3-138478544;