rs11240751

Positions:

• chr1-204492922-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.-85+1434T>C		intron_variant		ENST00000684373.1	NP_001364263.1
LOC124904584	XM_047439554.1	c.11+1161A>G		intron_variant			XP_047295510.1
PIK3C2B	NM_001377335.1	c.-884+1434T>C		intron_variant			NP_001364264.1
PIK3C2B	NM_002646.4	c.-884+1434T>C		intron_variant			NP_002637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.-85+1434T>C		intron_variant			NM_001377334.1	ENSP00000507222	P1
PIK3C2B	ENST00000429009.1	c.-201+1434T>C		intron_variant		2		ENSP00000409554

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

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.567

Alfa AF: 0.663 Hom.: 36675

Bravo AF: 0.533

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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