Variant rs1356413 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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.260

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:

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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 3-179226113-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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
PIK3CA	NM_006218.4 linkuse as main transcript	c.2495+73C>G		intron_variant		ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5 linkuse as main transcript	c.2495+73C>G		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.2495+73C>G		intron_variant		2	NM_006218.4	ENSP00000263967	P1

Frequencies

GnomAD3 genomes

AF:

0.0503

AC:

7649

AN:

151926

Hom.:

251

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0502

AC XY:

3728

AN XY:

74318

show subpopulations

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.:

Bravo

AF:

0.0542

Asia WGS

AF:

0.0540

AC:

186

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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