rs7519417

Variant names:

• chr1-204480824-T-C
• rs7519417
• NM_001377334.1:c.-84-10938A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-204480824-T-C
• chr1-204480824-T-G

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.-84-10938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,890 control chromosomes in the GnomAD database, including 31,730 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 0.63 (31730 hom., cov: 30)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 12 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2B	NM_001377334.1	MANE Select	c.-84-10938A>G		intron	N/A	NP_001364263.1
	PIK3C2B	NM_002646.4		c.-85+8992A>G		intron	N/A	NP_002637.3
	PIK3C2B	NM_001377335.1		c.-85+8992A>G		intron	N/A	NP_001364264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2B	ENST00000684373.1	MANE Select	c.-84-10938A>G		intron	N/A	ENSP00000507222.1
	PIK3C2B	ENST00000367187.7	TSL:1	c.-85+8992A>G		intron	N/A	ENSP00000356155.3
	PIK3C2B	ENST00000424712.6	TSL:1	c.-85+8992A>G		intron	N/A	ENSP00000400561.2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95290 AN: 151772 Hom.: 31728 Cov.: 30

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.627 AC: 95311 AN: 151890 Hom.: 31730 Cov.: 30 AF XY: 0.634 AC XY: 47054 AN XY: 74238

African (AFR) AF: 0.391 AC: 16176 AN: 41352

American (AMR) AF: 0.637 AC: 9721 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2354 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3657 AN: 5160

South Asian (SAS) AF: 0.670 AC: 3225 AN: 4814

European-Finnish (FIN) AF: 0.832 AC: 8800 AN: 10574

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49148 AN: 67946

Other (OTH) AF: 0.620 AC: 1307 AN: 2108

Alfa AF: 0.707 Hom.: 16549

Bravo AF: 0.603

Asia WGS AF: 0.641 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.53
PhyloP100		-1.5
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: rs7519417; hg19: chr1-204449952;