3-179148620-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+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,296 control chromosomes in the GnomAD database, including 2,841 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 0.18 (2825 hom., cov: 32)
  • Exomes 𝑓: 0.25 (16 hom.)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

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=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.-77+17C>T		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.-77+401C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-77+17C>T		intron_variant		2	NM_006218.4	P1
PIK3CA	ENST00000477735.1	c.-77+401C>T		intron_variant		4
PIK3CA	ENST00000643187.1	c.-77+17C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26634 AN: 151804 Hom.: 2822 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.250 AC: 94 AN: 376 Hom.: 16 Cov.: 0 AF XY: 0.248 AC XY: 65 AN XY: 262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.175 AC: 26644 AN: 151920 Hom.: 2825 Cov.: 32 AF XY: 0.172 AC XY: 12786 AN XY: 74282

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.172

Alfa AF: 0.209 Hom.: 601

Bravo AF: 0.166

Asia WGS AF: 0.112 AC: 388 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	13
Dann	Uncertain	0.98

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: rs2699887; hg19: chr3-178866408; COSMIC: COSV55874885; COSMIC: COSV55874885;