chr1-204437853-G-A

Variant names:

• chr1-204437853-G-A
• rs1877394
• NM_001377334.1:c.3516+1082C>T

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.3516+1082C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 152,278 control chromosomes in the GnomAD database, including 70 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 0.022 (70 hom., cov: 32)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 0 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]

PPP1R15B-AS1 (HGNC:55838): (PPP1R15B and PIK3C2B antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.3516+1082C>T		intron_variant	Intron 23 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.3516+1082C>T		intron_variant	Intron 25 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.3432+1082C>T		intron_variant	Intron 26 of 35		NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.3516+1082C>T		intron_variant	Intron 23 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3309 AN: 152160 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0217 AC: 3309 AN: 152278 Hom.: 70 Cov.: 32 AF XY: 0.0223 AC XY: 1661 AN XY: 74452

African (AFR) AF: 0.0202 AC: 839 AN: 41546

American (AMR) AF: 0.0180 AC: 275 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.127 AC: 658 AN: 5172

South Asian (SAS) AF: 0.0527 AC: 254 AN: 4822

European-Finnish (FIN) AF: 0.00602 AC: 64 AN: 10624

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1103 AN: 68032

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0199 Hom.: 78

Bravo AF: 0.0227

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		0.20
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: rs1877394; hg19: chr1-204406981;