NM_006219.3:c.2504+477G>A

Variant names:

• chr3-138681490-C-T
• rs12493155
• NM_006219.3:c.2504+477G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	NM_006219.3	MANE Select	c.2504+477G>A		intron	N/A	NP_006210.1	P42338
	PIK3CB	NM_001437286.1		c.2504+477G>A		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.2504+477G>A		intron	N/A	NP_001424216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.2504+477G>A		intron	N/A	ENSP00000501150.1	P42338
	PIK3CB	ENST00000477593.6	TSL:5	c.2504+477G>A		intron	N/A	ENSP00000418143.1	P42338
	PIK3CB	ENST00000894539.1		c.2504+477G>A		intron	N/A	ENSP00000564598.1

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

African (AFR) AF: 0.0859 AC: 3559 AN: 41428

American (AMR) AF: 0.541 AC: 8253 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3472

East Asian (EAS) AF: 0.448 AC: 2311 AN: 5162

South Asian (SAS) AF: 0.443 AC: 2130 AN: 4810

European-Finnish (FIN) AF: 0.473 AC: 4958 AN: 10484

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30798 AN: 67912

Other (OTH) AF: 0.373 AC: 786 AN: 2108

Alfa AF: 0.415 Hom.: 37265

Bravo AF: 0.355

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.81
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12493155; hg19: chr3-138400332;