rs9660554

Variant names:

• chr1-204430906-G-A
• rs9660554
• NM_001377334.1:c.4280+763C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204430906-G-A
• chr1-204430906-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377334.1(PIK3C2B):​c.4280+763C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 150,962 control chromosomes in the GnomAD database, including 5,133 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 0.25 (5133 hom., cov: 33)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.4280+763C>T		intron_variant	Intron 28 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.4280+763C>T		intron_variant	Intron 30 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.4196+763C>T		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+763C>T		intron_variant	Intron 28 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37187 AN: 150842 Hom.: 5116 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.247 AC: 37228 AN: 150962 Hom.: 5133 Cov.: 33 AF XY: 0.253 AC XY: 18669 AN XY: 73780

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.231

Alfa AF: 0.108 Hom.: 165

Bravo AF: 0.245

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs9660554; hg19: chr1-204400034;