3-179204486-C-A

Position:

• chr3-179204486-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006218.4(PIK3CA):​c.1060-17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,290,704 control chromosomes in the GnomAD database, including 223,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.64 (32593 hom., cov: 31)
  • Exomes 𝑓: 0.57 (191188 hom.)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.523

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]

PIK3CA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-179204486-C-A is Benign according to our data. Variant chr3-179204486-C-A is described in ClinVar as [Benign]. Clinvar id is 259957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179204486-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.1060-17C>A		intron_variant		ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.1060-17C>A		intron_variant			XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.1060-17C>A		intron_variant		2	NM_006218.4	ENSP00000263967.3

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96765 AN: 151954 Hom.: 32547 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.647

GnomAD3 exomes AF: 0.555 AC: 137275 AN: 247268 Hom.: 40044 AF XY: 0.555 AC XY: 74471 AN XY: 134178

Gnomad AFR exome AF: 0.865

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.560

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.572 AC: 651106 AN: 1138632 Hom.: 191188 Cov.: 15 AF XY: 0.571 AC XY: 332186 AN XY: 581320

Gnomad4 AFR exome AF: 0.873

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.565

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.585

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.637 AC: 96864 AN: 152072 Hom.: 32593 Cov.: 31 AF XY: 0.627 AC XY: 46590 AN XY: 74320

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.642

Alfa AF: 0.611 Hom.: 5421

Bravo AF: 0.653

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cowden syndrome 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Cowden syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.48
DANN	Benign	0.44
BranchPoint Hunter		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2699896; hg19: chr3-178922274; COSMIC: COSV55874930;