Variant 3-138684790-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_006219.3(PIK3CB):c.2150A>G(p.Asn717Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,612,038 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 11 hom. )

Consequence

PIK3CB
NM_006219.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.95

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, PIK3CB

BP4

Computational evidence support a benign effect (MetaRNN=0.009204358).

BP6

Variant 3-138684790-T-C is Benign according to our data. Variant chr3-138684790-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 717584.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 153 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CB	NM_006219.3 linkuse as main transcript	c.2150A>G	p.Asn717Ser	missense_variant	17/24	ENST00000674063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CB	ENST00000674063.1 linkuse as main transcript	c.2150A>G	p.Asn717Ser	missense_variant	17/24		NM_006219.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00166

AC:

412

AN:

248852

Hom.:

AF XY:

0.00203

AC XY:

273

AN XY:

134502

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00809

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00537

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00111

AC:

1624

AN:

1459726

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

953

AN XY:

726192

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00946

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00528

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000610

Gnomad4 OTH exome

AF:

0.00196

GnomAD4 genome

AF:

0.00100

AC:

153

AN:

152312

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00226

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.38

T;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.0029

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.75

T;.;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.2

N;N;N

REVEL

Uncertain

0.29

Sift

Benign

0.68

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0070

B;B;B

Vest4

0.12

MVP

0.38

MPC

0.40

ClinPred

0.013

GERP RS

5.8

Varity_R

0.16

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over