rs17849071

Positions:

• chr3-179218439-T-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.1664+105T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 808,138 control chromosomes in the GnomAD database, including 2,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (513 hom., cov: 32)
  • Exomes 𝑓: 0.071 (1740 hom.)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.397

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=-0.82).
• BP6: Variant 3-179218439-T-G is Benign according to our data. Variant chr3-179218439-T-G is described in ClinVar as [Benign]. Clinvar id is 1274886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.1664+105T>G		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.1664+105T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.1664+105T>G		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12110 AN: 151974 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0711 AC: 46626 AN: 656044 Hom.: 1740 AF XY: 0.0713 AC XY: 23849 AN XY: 334514

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.0496

Gnomad4 EAS exome AF: 0.0749

Gnomad4 SAS exome AF: 0.0781

Gnomad4 FIN exome AF: 0.0705

Gnomad4 NFE exome AF: 0.0683

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.0797 AC: 12128 AN: 152094 Hom.: 513 Cov.: 32 AF XY: 0.0806 AC XY: 5997 AN XY: 74362

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0925

Gnomad4 ASJ AF: 0.0465

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.0757 Hom.: 56

Bravo AF: 0.0841

Asia WGS AF: 0.0770 AC: 267 AN: 3468

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 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.65

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: rs17849071; hg19: chr3-178936227; COSMIC: COSV104381265; COSMIC: COSV104381265;