3-179166549-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.-77+17946C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,194 control chromosomes in the GnomAD database, including 2,944 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 0.19 (2944 hom., cov: 33)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.-77+17946C>T		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.-77+18330C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-77+17946C>T		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28193 AN: 152076 Hom.: 2943 Cov.: 33

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.185 AC: 28195 AN: 152194 Hom.: 2944 Cov.: 33 AF XY: 0.181 AC XY: 13484 AN XY: 74412

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.177

Alfa AF: 0.229 Hom.: 2577

Bravo AF: 0.177

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.7
Dann	Benign	0.67

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: rs2699905; hg19: chr3-178884337;