1-204434531-A-G

Variant names:

• chr1-204434531-A-G
• rs3747636
• NM_001377334.1:c.3594T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001377334.1(PIK3C2B):​c.3594T>C​(p.Asn1198Asn) 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
• Publications: 26 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 -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 rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.3594T>C	p.Asn1198Asn	synonymous_variant	Exon 24 of 33	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.3594T>C	p.Asn1198Asn	synonymous_variant	Exon 26 of 35		NP_002637.3
PIK3C2B	NM_001377335.1	c.3510T>C	p.Asn1170Asn	synonymous_variant	Exon 27 of 36		NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.3594T>C	p.Asn1198Asn	synonymous_variant	Exon 24 of 33		NM_001377334.1	ENSP00000507222.1

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

GnomAD2 exomes AF: 0.296 AC: 74261 AN: 250724 AF XY: 0.294

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 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

African (AFR) AF: 0.490 AC: 16393 AN: 33468

American (AMR) AF: 0.277 AC: 12385 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5427 AN: 26128

East Asian (EAS) AF: 0.518 AC: 20538 AN: 39680

South Asian (SAS) AF: 0.352 AC: 30314 AN: 86218

European-Finnish (FIN) AF: 0.324 AC: 17292 AN: 53400

Middle Eastern (MID) AF: 0.321 AC: 1852 AN: 5766

European-Non Finnish (NFE) AF: 0.217 AC: 241359 AN: 1111684

Other (OTH) AF: 0.263 AC: 15896 AN: 60380

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

African (AFR) AF: 0.490 AC: 20357 AN: 41526

American (AMR) AF: 0.283 AC: 4325 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2681 AN: 5162

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4822

European-Finnish (FIN) AF: 0.336 AC: 3551 AN: 10578

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15173 AN: 67994

Other (OTH) AF: 0.301 AC: 636 AN: 2114

Alfa AF: 0.256 Hom.: 22771

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
PhyloP100		-0.98
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: rs3747636; hg19: chr1-204403659; COSMIC: COSV65811498; COSMIC: COSV65811498;