3-138732510-T-G

Variant names:

• chr3-138732510-T-G
• rs10513055
• NM_006219.3:c.1050+851A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006219.3(PIK3CB):​c.1050+851A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,096 control chromosomes in the GnomAD database, including 2,468 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2468 hom., cov: 31)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	NM_006219.3	MANE Select	c.1050+851A>C		intron	N/A	NP_006210.1
	PIK3CB	NM_001437286.1		c.1050+851A>C		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.1050+851A>C		intron	N/A	NP_001424216.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.1050+851A>C		intron	N/A	ENSP00000501150.1
	PIK3CB	ENST00000289153.6	TSL:1	c.1050+851A>C		intron	N/A	ENSP00000289153.2
	PIK3CB	ENST00000477593.6	TSL:5	c.1050+851A>C		intron	N/A	ENSP00000418143.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25122 AN: 151978 Hom.: 2469 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25119 AN: 152096 Hom.: 2468 Cov.: 31 AF XY: 0.157 AC XY: 11678 AN XY: 74368

African (AFR) AF: 0.101 AC: 4178 AN: 41504

American (AMR) AF: 0.153 AC: 2344 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 948 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1368 AN: 10570

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15397 AN: 67970

Other (OTH) AF: 0.179 AC: 376 AN: 2106

Alfa AF: 0.199 Hom.: 5258

Bravo AF: 0.164

Asia WGS AF: 0.0340 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10513055; hg19: chr3-138451352;