3-179206019-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006218.4(PIK3CA):c.1145+1431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 151,626 control chromosomes in the GnomAD database, including 451 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 0.069 (451 hom., cov: 31)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.1145+1431C>T		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.1145+1431C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.1145+1431C>T		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10466 AN: 151546 Hom.: 450 Cov.: 31

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.0686

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

GnomAD4 genome AF: 0.0690 AC: 10463 AN: 151626 Hom.: 451 Cov.: 31 AF XY: 0.0675 AC XY: 4998 AN XY: 74048

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.0529

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.0703

Alfa AF: 0.0861 Hom.: 585

Bravo AF: 0.0687

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.61
Dann	Benign	0.48

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

Other links and lift over

dbSNP: rs2677764; hg19: chr3-178923807;