NM_006219.3:c.-121-1975T>C

Variant names:

• chr3-138798542-A-G
• rs6776585
• NM_006219.3:c.-121-1975T>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.-121-1975T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,066 control chromosomes in the GnomAD database, including 21,510 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 0.50 (21510 hom., cov: 32)
• Consequence: PIK3CB NM_006219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 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.-121-1975T>C		intron	N/A	NP_006210.1
	PIK3CB	NM_001437286.1		c.-17+36153T>C		intron	N/A	NP_001424215.1
	PIK3CB	NM_001437287.1		c.-188-1975T>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.-121-1975T>C		intron	N/A	ENSP00000501150.1
	PIK3CB	ENST00000477593.6	TSL:5	c.-17+36153T>C		intron	N/A	ENSP00000418143.1
	PIK3CB	ENST00000483968.5	TSL:3	c.-188-1975T>C		intron	N/A	ENSP00000419857.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76393 AN: 151948 Hom.: 21483 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.503 AC: 76464 AN: 152066 Hom.: 21510 Cov.: 32 AF XY: 0.488 AC XY: 36264 AN XY: 74360

African (AFR) AF: 0.723 AC: 29998 AN: 41484

American (AMR) AF: 0.384 AC: 5857 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3470

East Asian (EAS) AF: 0.0152 AC: 79 AN: 5190

South Asian (SAS) AF: 0.343 AC: 1658 AN: 4828

European-Finnish (FIN) AF: 0.337 AC: 3562 AN: 10580

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31768 AN: 67950

Other (OTH) AF: 0.500 AC: 1055 AN: 2110

Alfa AF: 0.472 Hom.: 8061

Bravo AF: 0.514

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.21
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: rs6776585; hg19: chr3-138517384;