rs7636454

chr3-179225280-A-Gchr3-179225280-A-T

Variant summary

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

The NM_006218.4(PIK3CA):c.2416+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,952 control chromosomes in the GnomAD database, including 5,072 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 0.24 (5072 hom., cov: 31)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.2416+459A>G		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.2416+459A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.2416+459A>G		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36290 AN: 151834 Hom.: 5067 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.239 AC: 36327 AN: 151952 Hom.: 5072 Cov.: 31 AF XY: 0.235 AC XY: 17445 AN XY: 74280

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.0999

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.250

Alfa AF: 0.210 Hom.: 629

Bravo AF: 0.257

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.5
Dann	Benign	0.78

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: rs7636454; hg19: chr3-178943068;