rs7641983

Positions:

• chr3-179168921-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+20318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 150,814 control chromosomes in the GnomAD database, including 5,820 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 (5820 hom., cov: 32)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.-77+20318C>T		intron_variant		ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.-77+20702C>T		intron_variant			XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-77+20318C>T		intron_variant		2	NM_006218.4	ENSP00000263967	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38186 AN: 150700 Hom.: 5809 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.254 AC: 38239 AN: 150814 Hom.: 5820 Cov.: 32 AF XY: 0.252 AC XY: 18535 AN XY: 73600

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.252

Alfa AF: 0.224 Hom.: 733

Bravo AF: 0.267

Asia WGS AF: 0.183 AC: 636 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.17

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: rs7641983; hg19: chr3-178886709;