rs3729679

chr3-179204642-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006218.4(PIK3CA):c.1145+54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 824,144 control chromosomes in the GnomAD database, including 115,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (26129 hom., cov: 30)
  • Exomes 𝑓: 0.51 (89839 hom.)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-179204642-A-G is Benign according to our data. Variant chr3-179204642-A-G is described in ClinVar as [Benign]. Clinvar id is 1236289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.1145+54A>G		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.1145+54A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.1145+54A>G		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86887 AN: 151762 Hom.: 26093 Cov.: 30

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.505 AC: 339709 AN: 672264 Hom.: 89839 AF XY: 0.505 AC XY: 179483 AN XY: 355440

Gnomad4 AFR exome AF: 0.765

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.573 AC: 86980 AN: 151880 Hom.: 26129 Cov.: 30 AF XY: 0.563 AC XY: 41777 AN XY: 74196

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.586

Alfa AF: 0.559 Hom.: 3590

Bravo AF: 0.589

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.32
Dann	Benign	0.74

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: rs3729679; hg19: chr3-178922430; COSMIC: COSV55874940;