dbSNP rs1517586: PIK3CA:c.-77+17517T>C (chr3-179166120-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006218.4(PIK3CA):c.-77+17517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,294 control chromosomes in the GnomAD database, including 464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.071 ( 464 hom., cov: 32)

Consequence

PIK3CA
NM_006218.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.577

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
megalencephaly-capillary malformation-polymicrogyria syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
vascular malformation
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 5
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

PIK3CA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4 link	c.-77+17517T>C		intron_variant	Intron 1 of 20	ENST00000263967.4	NP_006209.2	P42336Q4LE51
PIK3CA	XM_006713658.5 link	c.-77+17901T>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.-77+17517T>C		intron_variant	Intron 1 of 20	2	NM_006218.4	ENSP00000263967.3		P42336

Frequencies

GnomAD3 genomes

AF:

0.0709

AC:

10791

AN:

152176

Hom.:

463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.0755

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0675

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0988

Gnomad OTH

AF:

0.0707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0708

AC:

10789

AN:

152294

Hom.:

464

Cov.:

AF XY:

0.0693

AC XY:

5163

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0231

AC:

962

AN:

41564

American (AMR)

AF:

0.0752

AC:

1151

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

372

AN:

3470

East Asian (EAS)

AF:

0.0677

AC:

351

AN:

5188

South Asian (SAS)

AF:

0.0528

AC:

255

AN:

4828

European-Finnish (FIN)

AF:

0.0685

AC:

728

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0988

AC:

6719

AN:

68000

Other (OTH)

AF:

0.0724

AC:

153

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

516

1031

1547

2062

2578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0806

Hom.:

369

Bravo

AF:

0.0708

Asia WGS

AF:

0.0620

AC:

217

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.2

(source)

DANN

Benign

0.78

PhyloP100

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over