Genetic Variant PIK3CB:p.Asn717Ser (chr3-138684790-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 14/22 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, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.95

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

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 VariationId is 717584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 153 AD gene.

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.2150A>G	p.Asn717Ser	missense	Exon 17 of 24	NP_006210.1	P42338
PIK3CB	NM_001437286.1		c.2150A>G	p.Asn717Ser	missense	Exon 16 of 23	NP_001424215.1
PIK3CB	NM_001437287.1		c.2150A>G	p.Asn717Ser	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.2150A>G	p.Asn717Ser	missense	Exon 17 of 24	ENSP00000501150.1	P42338
PIK3CB	ENST00000477593.6	TSL:5	c.2150A>G	p.Asn717Ser	missense	Exon 16 of 23	ENSP00000418143.1	P42338
PIK3CB	ENST00000894539.1		c.2150A>G	p.Asn717Ser	missense	Exon 18 of 25	ENSP00000564598.1

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

GnomAD2 exomes

AF:

0.00166

AC:

412

AN:

248852

AF XY:

0.00203

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 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

African (AFR)

AF:

0.000509

AC:

AN:

33402

American (AMR)

AF:

0.00127

AC:

AN:

44236

Ashkenazi Jewish (ASJ)

AF:

0.00946

AC:

246

AN:

26014

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.00528

AC:

453

AN:

85788

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00937

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000610

AC:

678

AN:

1111124

Other (OTH)

AF:

0.00196

AC:

118

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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

AF:

0.00100

AC:

153

AN:

152312

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41568

American (AMR)

AF:

0.000981

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00455

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68032

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00135

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.38

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.0029

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.75

M_CAP

Benign

0.016

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.2

PhyloP100

1.9

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.29

Sift

Benign

0.68

Sift4G

Benign

0.49

Polyphen

0.0070

Vest4

0.12

MVP

0.38

MPC

0.40

ClinPred

0.013

GERP RS

5.8

Varity_R

0.16

gMVP

0.062

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over