3-138691104-T-C

Position:

• chr3-138691104-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006219.3(PIK3CB):​c.1932A>G​(p.Gln644=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,613,042 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (11 hom.)
• Consequence: PIK3CB NM_006219.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.81

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-138691104-T-C is Benign according to our data. Variant chr3-138691104-T-C is described in ClinVar as [Benign]. Clinvar id is 723991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BS2: High AC in GnomAd4 at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CB	NM_006219.3	c.1932A>G	p.Gln644=	synonymous_variant	15/24	ENST00000674063.1	NP_006210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CB	ENST00000674063.1	c.1932A>G	p.Gln644=	synonymous_variant	15/24		NM_006219.3	ENSP00000501150	P1

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00279

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00221 AC: 554 AN: 251008 Hom.: 1 AF XY: 0.00221 AC XY: 300 AN XY: 135676

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000556

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00281 AC: 4100 AN: 1460882 Hom.: 11 Cov.: 29 AF XY: 0.00279 AC XY: 2028 AN XY: 726804

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000738

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000545

Gnomad4 FIN exome AF: 0.00296

Gnomad4 NFE exome AF: 0.00338

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00162 AC: 246 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.00141 AC XY: 105 AN XY: 74326

Gnomad4 AFR AF: 0.000338

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00279

Gnomad4 OTH AF: 0.00239

Alfa AF: 0.00229 Hom.: 0

Bravo AF: 0.00159

EpiCase AF: 0.00241

EpiControl AF: 0.00273

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.7
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs34601499; hg19: chr3-138409946;