Variant chr3-179198731-T-C 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.-76-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 634,656 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 42 hom., cov: 32)

Exomes 𝑓: 0.014 ( 256 hom. )

Consequence

PIK3CA
NM_006218.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.27

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=-0.66).

BP6

Variant 3-179198731-T-C is Benign according to our data. Variant chr3-179198731-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1181592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179198731-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4 link	c.-76-19T>C		intron_variant	Intron 1 of 20	ENST00000263967.4	NP_006209.2	P42336Q4LE51
PIK3CA	XM_006713658.5 link	c.-76-19T>C		intron_variant	Intron 1 of 20		XP_006713721.1	P42336Q4LE51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4 link	c.-76-19T>C		intron_variant	Intron 1 of 20	2	NM_006218.4	ENSP00000263967.3		P42336

Frequencies

GnomAD3 genomes

AF:

0.00882

AC:

1343

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.00868

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00738

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.0136

AC:

6555

AN:

482340

Hom.:

256

Cov.:

AF XY:

0.0133

AC XY:

3320

AN XY:

249972

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.00524

Gnomad4 FIN exome

AF:

0.00253

Gnomad4 NFE exome

AF:

0.00746

Gnomad4 OTH exome

AF:

0.00954

GnomAD4 genome

AF:

0.00879

AC:

1339

AN:

152316

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

696

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.00869

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00738

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00860

Hom.:

Bravo

AF:

0.00954

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 04, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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