NM_006219.3:c.2687G>T

Variant names:

• chr3-138664015-C-A
• rs142933486
• NM_006219.3:c.2687G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006219.3(PIK3CB):​c.2687G>T​(p.Arg896Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000138 in 1,613,506 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: PIK3CB NM_006219.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.95
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0146299).
• BP6: Variant 3-138664015-C-A is Benign according to our data. Variant chr3-138664015-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 745706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 18 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	NM_006219.3	MANE Select	c.2687G>T	p.Arg896Leu	missense	Exon 21 of 24	NP_006210.1	P42338
	PIK3CB	NM_001437286.1		c.2687G>T	p.Arg896Leu	missense	Exon 20 of 23	NP_001424215.1
	PIK3CB	NM_001437287.1		c.2687G>T	p.Arg896Leu	missense	Exon 22 of 25	NP_001424216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.2687G>T	p.Arg896Leu	missense	Exon 21 of 24	ENSP00000501150.1	P42338
	PIK3CB	ENST00000477593.6	TSL:5	c.2687G>T	p.Arg896Leu	missense	Exon 20 of 23	ENSP00000418143.1	P42338
	PIK3CB	ENST00000894539.1		c.2687G>T	p.Arg896Leu	missense	Exon 22 of 25	ENSP00000564598.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000279 AC: 70 AN: 250726 AF XY: 0.000280

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00360

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000140 AC: 204 AN: 1461264 Hom.: 1 Cov.: 31 AF XY: 0.000142 AC XY: 103 AN XY: 726936

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.0000225 AC: 1 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00454 AC: 180 AN: 39690

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86136

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111842

Other (OTH) AF: 0.000116 AC: 7 AN: 60374

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74434

African (AFR) AF: 0.00 AC: 0 AN: 41532

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000151

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	-0.026	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.021	D
Polyphen		0.14	B
Vest4		0.65
MVP		0.80
MPC		1.4
ClinPred		0.28	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.59
gMVP		0.87
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs142933486; hg19: chr3-138382857;