3-138803794-T-C

Variant names:

• chr3-138803794-T-C
• rs1400266
• NM_006219.3:c.-121-7227A>G

Variant summary

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

The NM_006219.3(PIK3CB):​c.-121-7227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,908 control chromosomes in the GnomAD database, including 10,425 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 0.34 (10425 hom., cov: 31)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 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.-121-7227A>G		intron	N/A	NP_006210.1
	PIK3CB	NM_001437286.1		c.-17+30901A>G		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.-188-7227A>G		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.-121-7227A>G		intron	N/A	ENSP00000501150.1
	PIK3CB	ENST00000477593.6	TSL:5	c.-17+30901A>G		intron	N/A	ENSP00000418143.1
	PIK3CB	ENST00000483968.5	TSL:3	c.-188-7227A>G		intron	N/A	ENSP00000419857.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51723 AN: 151788 Hom.: 10427 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.340 AC: 51713 AN: 151908 Hom.: 10425 Cov.: 31 AF XY: 0.331 AC XY: 24581 AN XY: 74248

African (AFR) AF: 0.171 AC: 7075 AN: 41468

American (AMR) AF: 0.304 AC: 4627 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3468

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5178

South Asian (SAS) AF: 0.342 AC: 1644 AN: 4810

European-Finnish (FIN) AF: 0.337 AC: 3549 AN: 10542

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31516 AN: 67904

Other (OTH) AF: 0.376 AC: 795 AN: 2114

Alfa AF: 0.388 Hom.: 5859

Bravo AF: 0.329

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.53
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1400266; hg19: chr3-138522636;