rs1356413

Positions:

• chr3-179226113-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006218.4(PIK3CA):​c.2495+73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 760,876 control chromosomes in the GnomAD database, including 1,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (252 hom., cov: 32)
  • Exomes 𝑓: 0.050 (876 hom.)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.260

Genes affected

PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-179226113-C-G is Benign according to our data. Variant chr3-179226113-C-G is described in ClinVar as [Benign]. Clinvar id is 1269218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.2495+73C>G		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.2495+73C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.2495+73C>G		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7649 AN: 151926 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0742

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.0504 AC: 30705 AN: 608832 Hom.: 876 AF XY: 0.0501 AC XY: 16299 AN XY: 325054

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.0776

Gnomad4 ASJ exome AF: 0.0773

Gnomad4 EAS exome AF: 0.0545

Gnomad4 SAS exome AF: 0.0491

Gnomad4 FIN exome AF: 0.0350

Gnomad4 NFE exome AF: 0.0464

Gnomad4 OTH exome AF: 0.0533

GnomAD4 genome AF: 0.0504 AC: 7658 AN: 152044 Hom.: 252 Cov.: 32 AF XY: 0.0502 AC XY: 3728 AN XY: 74318

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0742

Gnomad4 EAS AF: 0.0521

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0439 Hom.: 22

Bravo AF: 0.0542

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.34

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: rs1356413; hg19: chr3-178943901; COSMIC: COSV104381260; COSMIC: COSV104381260;