dbSNP rs7641983: PIK3CA:c.-77+20318C>T (chr3-179168921-C-T) – 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+20318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 150,814 control chromosomes in the GnomAD database, including 5,820 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 0.25 ( 5820 hom., cov: 32)

Consequence

PIK3CA
NM_006218.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

7 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:

ENSG00000201957 (HGNC:):

ENSG00000201957 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4 link	c.-77+20318C>T	intron_variant	Intron 1 of 20	ENST00000263967.4	NP_006209.2	P42336Q4LE51
PIK3CA	XM_006713658.5 link	c.-77+20702C>T	intron_variant	Intron 1 of 20		XP_006713721.1	P42336Q4LE51
LOC124900560	XR_007096309.1 link	n.*162G>A	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4 link	c.-77+20318C>T		intron_variant	Intron 1 of 20	2	NM_006218.4	ENSP00000263967.3		P42336

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38186

AN:

150700

Hom.:

5809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.255

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

GnomAD4 genome

AF:

0.254

AC:

38239

AN:

150814

Hom.:

5820

Cov.:

AF XY:

0.252

AC XY:

18535

AN XY:

73600

show subpopulations

African (AFR)

AF:

0.424

AC:

17461

AN:

41174

American (AMR)

AF:

0.228

AC:

3454

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

864

AN:

3458

East Asian (EAS)

AF:

0.102

AC:

520

AN:

5112

South Asian (SAS)

AF:

0.243

AC:

1155

AN:

4750

European-Finnish (FIN)

AF:

0.163

AC:

1672

AN:

10262

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12223

AN:

67620

Other (OTH)

AF:

0.252

AC:

525

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1339

2678

4018

5357

6696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.230

Hom.:

802

Bravo

AF:

0.267

Asia WGS

AF:

0.183

AC:

636

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.83

(source)

DANN

Benign

0.17

PhyloP100

-1.0

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