chr1-204430938-A-G

Variant names:

• chr1-204430938-A-G
• rs9661807
• NM_001377334.1:c.4280+731T>C

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.4280+731T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,166 control chromosomes in the GnomAD database, including 5,675 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 0.26 (5675 hom., cov: 33)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.4280+731T>C		intron_variant	Intron 28 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.4280+731T>C		intron_variant	Intron 30 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.4196+731T>C		intron_variant	Intron 31 of 35		NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.4280+731T>C		intron_variant	Intron 28 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38796 AN: 152048 Hom.: 5657 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.255 AC: 38841 AN: 152166 Hom.: 5675 Cov.: 33 AF XY: 0.261 AC XY: 19438 AN XY: 74406

African (AFR) AF: 0.354 AC: 14681 AN: 41484

American (AMR) AF: 0.238 AC: 3638 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2874 AN: 5184

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2685 AN: 10596

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11979 AN: 67998

Other (OTH) AF: 0.239 AC: 504 AN: 2112

Alfa AF: 0.225 Hom.: 480

Bravo AF: 0.257

Asia WGS AF: 0.366 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.32
PhyloP100		-0.38
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: rs9661807; hg19: chr1-204400066;