3-179214763-C-T

Variant names:

• chr3-179214763-C-T
• rs12494623
• NM_006218.4:c.1540-3447C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006218.4(PIK3CA):​c.1540-3447C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,794 control chromosomes in the GnomAD database, including 26,040 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 0.57 (26040 hom., cov: 30)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 3 publications found

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]

PIK3CA Gene-Disease associations (from GenCC):

• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• megalencephaly-capillary malformation-polymicrogyria syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• vascular malformation

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Cowden disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Cowden syndrome 5

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006218.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CA	NM_006218.4	MANE Select	c.1540-3447C>T		intron	N/A	NP_006209.2	P42336

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CA	ENST00000263967.4	TSL:2 MANE Select	c.1540-3447C>T		intron	N/A	ENSP00000263967.3	P42336
	PIK3CA	ENST00000955190.1		c.1570-3447C>T		intron	N/A	ENSP00000625249.1
	PIK3CA	ENST00000876545.1		c.1540-3447C>T		intron	N/A	ENSP00000546604.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86743 AN: 151676 Hom.: 26003 Cov.: 30

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.572 AC: 86837 AN: 151794 Hom.: 26040 Cov.: 30 AF XY: 0.563 AC XY: 41734 AN XY: 74178

African (AFR) AF: 0.756 AC: 31273 AN: 41386

American (AMR) AF: 0.509 AC: 7757 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1979 AN: 3464

East Asian (EAS) AF: 0.221 AC: 1145 AN: 5174

South Asian (SAS) AF: 0.468 AC: 2245 AN: 4802

European-Finnish (FIN) AF: 0.434 AC: 4561 AN: 10506

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35772 AN: 67898

Other (OTH) AF: 0.583 AC: 1233 AN: 2114

Alfa AF: 0.465 Hom.: 6832

Bravo AF: 0.588

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.1
DANN	Benign	0.24
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12494623; hg19: chr3-178932551;