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GeneBe

3-138655397-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_006219.3(PIK3CB):c.3205A>C(p.Arg1069=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,614,088 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 11 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 103 hom. )

Consequence

PIK3CB
NM_006219.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.504
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-138655397-T-G is Benign according to our data. Variant chr3-138655397-T-G is described in ClinVar as [Benign]. Clinvar id is 731809.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.504 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3CBNM_006219.3 linkuse as main transcriptc.3205A>C p.Arg1069= synonymous_variant 24/24 ENST00000674063.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3CBENST00000674063.1 linkuse as main transcriptc.3205A>C p.Arg1069= synonymous_variant 24/24 NM_006219.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00250
AC:
381
AN:
152202
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0677
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00566
AC:
1421
AN:
251052
Hom.:
58
AF XY:
0.00542
AC XY:
735
AN XY:
135670
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0721
Gnomad SAS exome
AF:
0.00206
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00201
AC:
2940
AN:
1461768
Hom.:
103
Cov.:
30
AF XY:
0.00207
AC XY:
1507
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0627
Gnomad4 SAS exome
AF:
0.00234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000827
Gnomad4 OTH exome
AF:
0.00245
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00250
AC:
381
AN:
152320
Hom.:
11
Cov.:
32
AF XY:
0.00289
AC XY:
215
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0679
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000455
Hom.:
2
Bravo
AF:
0.00336
Asia WGS
AF:
0.0240
AC:
82
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
5.7
Dann
Benign
0.56

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

LitVar

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

Other links and lift over

dbSNP: rs28763907; hg19: chr3-138374239; COSMIC: COSV56686416; COSMIC: COSV56686416; API