rs145339552

Variant names:

• chr3-138682017-T-C
• rs145339552
• NM_006219.3:c.2454A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-138682017-T-C
• chr3-138682017-T-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The NM_006219.3(PIK3CB):​c.2454A>G​(p.Gln818Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,612,246 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: PIK3CB NM_006219.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.362
• Publications: 2 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 -7 ACMG points.

• BP6: Variant 3-138682017-T-C is Benign according to our data. Variant chr3-138682017-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 740906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.362 with no splicing effect.
• BS2: High AC in GnomAd4 at 32 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.2454A>G	p.Gln818Gln	synonymous	Exon 19 of 24	NP_006210.1	P42338
	PIK3CB	NM_001437286.1		c.2454A>G	p.Gln818Gln	synonymous	Exon 18 of 23	NP_001424215.1
	PIK3CB	NM_001437287.1		c.2454A>G	p.Gln818Gln	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.2454A>G	p.Gln818Gln	synonymous	Exon 19 of 24	ENSP00000501150.1	P42338
	PIK3CB	ENST00000477593.6	TSL:5	c.2454A>G	p.Gln818Gln	synonymous	Exon 18 of 23	ENSP00000418143.1	P42338
	PIK3CB	ENST00000894539.1		c.2454A>G	p.Gln818Gln	synonymous	Exon 20 of 25	ENSP00000564598.1

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151944 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000475

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000228 AC: 57 AN: 250100 AF XY: 0.000207

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000424

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000213 AC: 311 AN: 1460302 Hom.: 2 Cov.: 30 AF XY: 0.000201 AC XY: 146 AN XY: 726360

African (AFR) AF: 0.0000898 AC: 3 AN: 33408

American (AMR) AF: 0.0000225 AC: 1 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53398

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5756

European-Non Finnish (NFE) AF: 0.000221 AC: 246 AN: 1111292

Other (OTH) AF: 0.000464 AC: 28 AN: 60330

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151944 Hom.: 0 Cov.: 32 AF XY: 0.000243 AC XY: 18 AN XY: 74202

African (AFR) AF: 0.000121 AC: 5 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15248

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.000475 AC: 5 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.000181

Asia WGS AF: 0.000289 AC: 1 AN: 3476

EpiCase AF: 0.000219

EpiControl AF: 0.0000594

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
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.48
DANN	Benign	0.33
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs145339552; hg19: chr3-138400859;