Genetic Variant PIK3CB:p.Ile767Val (chr3-138684641-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006219.3(PIK3CB):c.2299A>G(p.Ile767Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I767F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PIK3CB
NM_006219.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26

Publications

4 publications found

Variant links:

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]

PIK3CB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1542078).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3CB	NM_006219.3	MANE Select	c.2299A>G	p.Ile767Val	missense	Exon 17 of 24	NP_006210.1	P42338
PIK3CB	NM_001437286.1		c.2299A>G	p.Ile767Val	missense	Exon 16 of 23	NP_001424215.1
PIK3CB	NM_001437287.1		c.2299A>G	p.Ile767Val	missense	Exon 18 of 25	NP_001424216.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3CB	ENST00000674063.1	MANE Select	c.2299A>G	p.Ile767Val	missense	Exon 17 of 24	ENSP00000501150.1	P42338
PIK3CB	ENST00000477593.6	TSL:5	c.2299A>G	p.Ile767Val	missense	Exon 16 of 23	ENSP00000418143.1	P42338
PIK3CB	ENST00000894539.1		c.2299A>G	p.Ile767Val	missense	Exon 18 of 25	ENSP00000564598.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

245286

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456320

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33134

American (AMR)

AF:

0.00

AC:

AN:

43450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25828

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110034

Other (OTH)

AF:

0.00

AC:

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.19

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.091

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

M_CAP

Benign

0.023

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.4

PhyloP100

2.3

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.090

REVEL

Benign

0.15

Sift

Benign

0.17

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.11

MutPred

0.34

Gain of sheet (P = 0.1451)

MVP

0.45

MPC

0.41

ClinPred

0.20

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over