Genetic Variant PIK3CB:c.1400-297A>G (chr3-138707586-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006219.3(PIK3CB):c.1400-297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,103,350 control chromosomes in the GnomAD database, including 166,085 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 0.58 ( 26124 hom., cov: 32)

Exomes 𝑓: 0.54 ( 139961 hom. )

Consequence

PIK3CB
NM_006219.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.87

Publications

6 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

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 link	c.1400-297A>G		intron_variant	Intron 10 of 23	ENST00000674063.1	NP_006210.1	P42338

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CB	ENST00000674063.1 link	c.1400-297A>G		intron_variant	Intron 10 of 23		NM_006219.3	ENSP00000501150.1		P42338

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87666

AN:

151996

Hom.:

26089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.658

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.551

GnomAD4 exome

AF:

0.539

AC:

512304

AN:

951236

Hom.:

139961

Cov.:

AF XY:

0.539

AC XY:

241229

AN XY:

447808

show subpopulations

African (AFR)

AF:

0.545

AC:

10074

AN:

18490

American (AMR)

AF:

0.692

AC:

2799

AN:

4042

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

4651

AN:

9808

East Asian (EAS)

AF:

0.985

AC:

9849

AN:

10004

South Asian (SAS)

AF:

0.638

AC:

19229

AN:

30160

European-Finnish (FIN)

AF:

0.661

AC:

4901

AN:

7412

Middle Eastern (MID)

AF:

0.482

AC:

1059

AN:

2196

European-Non Finnish (NFE)

AF:

0.528

AC:

439848

AN:

833804

Other (OTH)

AF:

0.563

AC:

19894

AN:

35320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

9125

18251

27376

36502

45627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15548

31096

46644

62192

77740

<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:

0.577

AC:

87757

AN:

152114

Hom.:

26124

Cov.:

AF XY:

0.589

AC XY:

43773

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.555

AC:

23027

AN:

41498

American (AMR)

AF:

0.642

AC:

9812

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1672

AN:

3472

East Asian (EAS)

AF:

0.985

AC:

5099

AN:

5178

South Asian (SAS)

AF:

0.658

AC:

3171

AN:

4820

European-Finnish (FIN)

AF:

0.663

AC:

7010

AN:

10570

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36232

AN:

67966

Other (OTH)

AF:

0.556

AC:

1177

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1867

3734

5602

7469

9336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.555

Hom.:

31238

Bravo

AF:

0.575

Asia WGS

AF:

0.815

AC:

2831

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.10

(source)

DANN

Benign

0.42

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over