Variant rs41273619 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.80

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PIK3CA	NM_006218.4 linkuse as main transcript	c.1747-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5 linkuse as main transcript	c.1747-13T>C		splice_polypyrimidine_tract_variant, intron_variant			XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4 linkuse as main transcript	c.1747-13T>C		splice_polypyrimidine_tract_variant, intron_variant		2	NM_006218.4	ENSP00000263967	P1

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

7748

AN:

151960

Hom.:

212

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0471

AC XY:

26727

AN XY:

567718

show subpopulations

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.:

AF XY:

0.0508

AC XY:

3774

AN XY:

74354

show subpopulations

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.:

Bravo

AF:

0.0506

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over