rs41273619

chr3-179219558-T-C

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.1747-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,268,272 control chromosomes in the GnomAD database, including 1,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (211 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1367 hom.)
• Consequence: PIK3CA NM_006218.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.80

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-179219558-T-C is Benign according to our data. Variant chr3-179219558-T-C is described in ClinVar as [Benign]. Clinvar id is 259959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179219558-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.1747-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.1747-13T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.1747-13T>C		splice_polypyrimidine_tract_variant, intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7748 AN: 151960 Hom.: 212 Cov.: 32

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0869

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0699

GnomAD3 exomes AF: 0.0469 AC: 10621 AN: 226646 Hom.: 335 AF XY: 0.0470 AC XY: 5800 AN XY: 123522

Gnomad AFR exome AF: 0.0426

Gnomad AMR exome AF: 0.0379

Gnomad ASJ exome AF: 0.0893

Gnomad EAS exome AF: 0.0000593

Gnomad SAS exome AF: 0.0123

Gnomad FIN exome AF: 0.0655

Gnomad NFE exome AF: 0.0594

Gnomad OTH exome AF: 0.0524

GnomAD4 exome AF: 0.0478 AC: 53307 AN: 1116194 Hom.: 1367 Cov.: 14 AF XY: 0.0471 AC XY: 26727 AN XY: 567718

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.0394

Gnomad4 ASJ exome AF: 0.0862

Gnomad4 EAS exome AF: 0.0000529

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.0609

Gnomad4 NFE exome AF: 0.0518

Gnomad4 OTH exome AF: 0.0501

GnomAD4 genome AF: 0.0510 AC: 7749 AN: 152078 Hom.: 211 Cov.: 32 AF XY: 0.0508 AC XY: 3774 AN XY: 74354

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.0869

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0565 Hom.: 79

Bravo AF: 0.0506

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 06, 2018	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	11
Dann	Benign	0.59

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: rs41273619; hg19: chr3-178937346; COSMIC: COSV55916313;