rs7644648

Positions:

• chr3-179172862-A-G

Variant summary

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

The NM_006218.4(PIK3CA):​c.-77+24259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,110 control chromosomes in the GnomAD database, including 5,812 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 0.25 (5812 hom., cov: 31)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.-77+24259A>G		intron_variant		ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.-77+24643A>G		intron_variant			XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-77+24259A>G		intron_variant		2	NM_006218.4	ENSP00000263967	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38224 AN: 151992 Hom.: 5801 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.252 AC: 38277 AN: 152110 Hom.: 5812 Cov.: 31 AF XY: 0.250 AC XY: 18556 AN XY: 74356

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.249

Alfa AF: 0.218 Hom.: 564

Bravo AF: 0.267

Asia WGS AF: 0.183 AC: 634 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.41

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: rs7644648; hg19: chr3-178890650;