rs7636454

Variant names:

• chr3-179225280-A-G
• rs7636454
• NM_006218.4:c.2416+459A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-179225280-A-G
• chr3-179225280-A-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.2416+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,952 control chromosomes in the GnomAD database, including 5,072 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 0.24 (5072 hom., cov: 31)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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.2416+459A>G		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.2416+459A>G		intron	N/A	ENSP00000263967.3	P42336
	PIK3CA	ENST00000955190.1		c.2446+459A>G		intron	N/A	ENSP00000625249.1
	PIK3CA	ENST00000876545.1		c.2416+459A>G		intron	N/A	ENSP00000546604.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36290 AN: 151834 Hom.: 5067 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.239 AC: 36327 AN: 151952 Hom.: 5072 Cov.: 31 AF XY: 0.235 AC XY: 17445 AN XY: 74280

African (AFR) AF: 0.384 AC: 15903 AN: 41402

American (AMR) AF: 0.225 AC: 3427 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3466

East Asian (EAS) AF: 0.0999 AC: 518 AN: 5184

South Asian (SAS) AF: 0.108 AC: 522 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1678 AN: 10560

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12532 AN: 67954

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.215 Hom.: 685

Bravo AF: 0.257

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		-0.0090
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: rs7636454; hg19: chr3-178943068;