rs7640662

Positions:

• chr3-179184213-C-G

Variant summary

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

The NM_006218.4(PIK3CA):​c.-76-14537C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,292 control chromosomes in the GnomAD database, including 982 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 0.10 (982 hom., cov: 32)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.-76-14537C>G		intron_variant		ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.-76-14537C>G		intron_variant			XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-76-14537C>G		intron_variant		2	NM_006218.4	ENSP00000263967	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15277 AN: 152174 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.0969

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

GnomAD4 genome AF: 0.100 AC: 15276 AN: 152292 Hom.: 982 Cov.: 32 AF XY: 0.0986 AC XY: 7347 AN XY: 74478

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.123 Hom.: 163

Bravo AF: 0.0903

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.3
DANN	Benign	0.64

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: rs7640662; hg19: chr3-178902001;