rs9838411

chr3-179169899-G-A

Variant summary

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

The NM_006218.4(PIK3CA):c.-77+21296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,140 control chromosomes in the GnomAD database, including 5,621 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 (5621 hom., cov: 33)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.-77+21296G>A		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.-77+21680G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-77+21296G>A		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37196 AN: 152022 Hom.: 5610 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.245 AC: 37251 AN: 152140 Hom.: 5621 Cov.: 33 AF XY: 0.241 AC XY: 17943 AN XY: 74398

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.0974

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.247

Alfa AF: 0.220 Hom.: 720

Bravo AF: 0.264

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	11
Dann	Benign	0.88

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: rs9838411; hg19: chr3-178887687;