1-204483386-A-T

Variant names:

• chr1-204483386-A-T
• rs4951384
• NM_001377334.1:c.-85+10970T>A

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+10970T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 137,956 control chromosomes in the GnomAD database, including 30,945 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 0.68 (30945 hom., cov: 27)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.-85+10970T>A		intron_variant	Intron 1 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.-85+6430T>A		intron_variant	Intron 3 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.-85+6430T>A		intron_variant	Intron 3 of 35		NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.-85+10970T>A		intron_variant	Intron 1 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 93518 AN: 137854 Hom.: 30941 Cov.: 27

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.762

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.678 AC: 93541 AN: 137956 Hom.: 30945 Cov.: 27 AF XY: 0.684 AC XY: 46091 AN XY: 67364

African (AFR) AF: 0.425 AC: 15241 AN: 35846

American (AMR) AF: 0.708 AC: 9599 AN: 13554

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2243 AN: 3112

East Asian (EAS) AF: 0.765 AC: 3603 AN: 4708

South Asian (SAS) AF: 0.742 AC: 3198 AN: 4312

European-Finnish (FIN) AF: 0.850 AC: 8519 AN: 10022

Middle Eastern (MID) AF: 0.761 AC: 201 AN: 264

European-Non Finnish (NFE) AF: 0.772 AC: 48921 AN: 63376

Other (OTH) AF: 0.688 AC: 1297 AN: 1884

Alfa AF: 0.671 Hom.: 4206

Bravo AF: 0.594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.73
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4951384; hg19: chr1-204452514;