rs201051343

Variant names:

• chr3-138682038-T-C
• rs201051343
• NM_006219.3:c.2433A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-138682038-T-C
• chr3-138682038-T-A
• chr3-138682038-T-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006219.3(PIK3CB):​c.2433A>G​(p.Arg811Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,609,366 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (13 hom.)
• Consequence: PIK3CB NM_006219.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.508
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.037).
• BP6: Variant 3-138682038-T-C is Benign according to our data. Variant chr3-138682038-T-C is described in ClinVar as Benign. ClinVar VariationId is 722053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.508 with no splicing effect.
• BS2: High AC in GnomAd4 at 61 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.2433A>G	p.Arg811Arg	synonymous	Exon 19 of 24	NP_006210.1	P42338
	PIK3CB	NM_001437286.1		c.2433A>G	p.Arg811Arg	synonymous	Exon 18 of 23	NP_001424215.1
	PIK3CB	NM_001437287.1		c.2433A>G	p.Arg811Arg	synonymous	Exon 20 of 25	NP_001424216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.2433A>G	p.Arg811Arg	synonymous	Exon 19 of 24	ENSP00000501150.1	P42338
	PIK3CB	ENST00000477593.6	TSL:5	c.2433A>G	p.Arg811Arg	synonymous	Exon 18 of 23	ENSP00000418143.1	P42338
	PIK3CB	ENST00000894539.1		c.2433A>G	p.Arg811Arg	synonymous	Exon 20 of 25	ENSP00000564598.1

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00118 AC: 293 AN: 248152 AF XY: 0.00158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000592

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000284

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000640 AC: 932 AN: 1457108 Hom.: 13 Cov.: 30 AF XY: 0.000869 AC XY: 630 AN XY: 724842

African (AFR) AF: 0.0000601 AC: 2 AN: 33284

American (AMR) AF: 0.0000905 AC: 4 AN: 44196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39578

South Asian (SAS) AF: 0.00803 AC: 684 AN: 85208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00783 AC: 45 AN: 5750

European-Non Finnish (NFE) AF: 0.000130 AC: 144 AN: 1109376

Other (OTH) AF: 0.000847 AC: 51 AN: 60246

GnomAD4 genome AF: 0.000401 AC: 61 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41554

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000223 Hom.: 0

Bravo AF: 0.000166

Asia WGS AF: 0.00376 AC: 13 AN: 3476

EpiCase AF: 0.000329

EpiControl AF: 0.000416

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.9
DANN	Benign	0.63
PhyloP100		-0.51
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201051343; hg19: chr3-138400880; COSMIC: COSV105860686; COSMIC: COSV105860686;