rs3747636

chr1-204434531-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001377334.1(PIK3C2B):c.3594T>C(p.Asn1198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,574 control chromosomes in the GnomAD database, including 58,155 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 0.33 (9186 hom., cov: 33)
  • Exomes 𝑓: 0.25 (48969 hom.)
• Consequence: PIK3C2B NM_001377334.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C2B	NM_001377334.1	c.3594T>C	p.Asn1198=	synonymous_variant	24/33	ENST00000684373.1
PIK3C2B	NM_002646.4	c.3594T>C	p.Asn1198=	synonymous_variant	26/35
PIK3C2B	NM_001377335.1	c.3510T>C	p.Asn1170=	synonymous_variant	27/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.3594T>C	p.Asn1198=	synonymous_variant	24/33		NM_001377334.1	P1
PPP1R15B-AS1	ENST00000443515.1	n.147-806A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49499 AN: 152050 Hom.: 9168 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.296 AC: 74261 AN: 250724 Hom.: 12280 AF XY: 0.294 AC XY: 39833 AN XY: 135518

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.526

Gnomad SAS exome AF: 0.353

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.247 AC: 361456 AN: 1461402 Hom.: 48969 Cov.: 34 AF XY: 0.250 AC XY: 181938 AN XY: 726992

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.326 AC: 49562 AN: 152172 Hom.: 9186 Cov.: 33 AF XY: 0.332 AC XY: 24710 AN XY: 74384

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.301

Alfa AF: 0.245 Hom.: 10644

Bravo AF: 0.325

Asia WGS AF: 0.398 AC: 1382 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.9
Dann	Benign	0.49

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: rs3747636; hg19: chr1-204403659; COSMIC: COSV65811498; COSMIC: COSV65811498;