chr1-204475907-T-C

Variant names:

• chr1-204475907-T-C
• rs1553920
• NM_001377334.1:c.-84-6021A>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.-84-6021A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,120 control chromosomes in the GnomAD database, including 59,656 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 0.87 (59656 hom., cov: 30)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.32
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.-84-6021A>G		intron_variant	Intron 1 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.-84-6021A>G		intron_variant	Intron 3 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.-84-6021A>G		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.-84-6021A>G		intron_variant	Intron 1 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132663 AN: 152002 Hom.: 59640 Cov.: 30

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.872 AC: 132718 AN: 152120 Hom.: 59656 Cov.: 30 AF XY: 0.872 AC XY: 64862 AN XY: 74362

African (AFR) AF: 0.643 AC: 26652 AN: 41444

American (AMR) AF: 0.908 AC: 13900 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3368 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4044 AN: 5146

South Asian (SAS) AF: 0.916 AC: 4406 AN: 4812

European-Finnish (FIN) AF: 0.965 AC: 10237 AN: 10606

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67034 AN: 68020

Other (OTH) AF: 0.898 AC: 1898 AN: 2114

Alfa AF: 0.960 Hom.: 43495

Bravo AF: 0.857

Asia WGS AF: 0.847 AC: 2947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.46
PhyloP100		-7.3
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: rs1553920; hg19: chr1-204445035;