3-179175241-A-G

Variant names:

• chr3-179175241-A-G
• rs7651265
• NM_006218.4:c.-76-23509A>G

Variant summary

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

The NM_006218.4(PIK3CA):​c.-76-23509A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,062 control chromosomes in the GnomAD database, including 1,228 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 0.13 (1228 hom., cov: 32)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.-76-23509A>G		intron_variant	Intron 1 of 20	ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.-76-23509A>G		intron_variant	Intron 1 of 20		XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-76-23509A>G		intron_variant	Intron 1 of 20	2	NM_006218.4	ENSP00000263967.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19098 AN: 151946 Hom.: 1229 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.126 AC: 19117 AN: 152062 Hom.: 1228 Cov.: 32 AF XY: 0.127 AC XY: 9431 AN XY: 74322

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0983

Gnomad4 SAS AF: 0.0887

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.130

Alfa AF: 0.119 Hom.: 957

Bravo AF: 0.129

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.43

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: rs7651265; hg19: chr3-178893029;