rs11240751

Variant names:

• chr1-204492922-A-G
• rs11240751
• NM_001377334.1:c.-85+1434T>C

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.-85+1434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,080 control chromosomes in the GnomAD database, including 27,393 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 0.56 (27393 hom., cov: 31)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 16 publications found

Genes affected

PIK3C2B (HGNC:8972): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]

LOC124904584 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377334.1. 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
	PIK3C2B	NM_001377334.1	MANE Select	c.-85+1434T>C		intron	N/A	NP_001364263.1
	PIK3C2B	NM_002646.4		c.-884+1434T>C		intron	N/A	NP_002637.3
	PIK3C2B	NM_001377335.1		c.-884+1434T>C		intron	N/A	NP_001364264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2B	ENST00000684373.1	MANE Select	c.-85+1434T>C		intron	N/A	ENSP00000507222.1
	PIK3C2B	ENST00000920831.1		c.-85+1434T>C		intron	N/A	ENSP00000590890.1
	PIK3C2B	ENST00000429009.1	TSL:2	c.-201+1434T>C		intron	N/A	ENSP00000409554.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85650 AN: 151962 Hom.: 27387 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.563 AC: 85661 AN: 152080 Hom.: 27393 Cov.: 31 AF XY: 0.570 AC XY: 42404 AN XY: 74334

African (AFR) AF: 0.239 AC: 9907 AN: 41508

American (AMR) AF: 0.596 AC: 9093 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2110 AN: 3466

East Asian (EAS) AF: 0.701 AC: 3612 AN: 5154

South Asian (SAS) AF: 0.608 AC: 2928 AN: 4814

European-Finnish (FIN) AF: 0.814 AC: 8617 AN: 10592

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47316 AN: 67970

Other (OTH) AF: 0.567 AC: 1199 AN: 2114

Alfa AF: 0.651 Hom.: 52445

Bravo AF: 0.533

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.52
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs11240751; hg19: chr1-204462050; COSMIC: COSV65814045;