rs7621329

Variant names:

• chr3-179157086-C-T
• rs7621329
• NM_006218.4:c.-77+8483C>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.-77+8483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,034 control chromosomes in the GnomAD database, including 5,815 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 (5815 hom., cov: 32)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 20 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)
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.-77+8483C>T		intron_variant	Intron 1 of 20	ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.-77+8867C>T		intron_variant	Intron 1 of 20		XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-77+8483C>T		intron_variant	Intron 1 of 20	2	NM_006218.4	ENSP00000263967.3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38242 AN: 151916 Hom.: 5805 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.252 AC: 38295 AN: 152034 Hom.: 5815 Cov.: 32 AF XY: 0.250 AC XY: 18575 AN XY: 74320

African (AFR) AF: 0.421 AC: 17464 AN: 41440

American (AMR) AF: 0.227 AC: 3464 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3466

East Asian (EAS) AF: 0.102 AC: 527 AN: 5182

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10580

Middle Eastern (MID) AF: 0.317 AC: 92 AN: 290

European-Non Finnish (NFE) AF: 0.180 AC: 12235 AN: 67958

Other (OTH) AF: 0.250 AC: 528 AN: 2114

Alfa AF: 0.205 Hom.: 1830

Bravo AF: 0.267

Asia WGS AF: 0.183 AC: 637 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.71
PhyloP100		-0.78
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: rs7621329; hg19: chr3-178874874;