rs870995

Variant names:

• chr3-179195218-C-A
• rs870995
• NM_006218.4:c.-76-3532C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-179195218-C-A
• chr3-179195218-C-G

Variant summary

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

The NM_006218.4(PIK3CA):​c.-76-3532C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 150,682 control chromosomes in the GnomAD database, including 26,049 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. The gene PIK3CA is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.57 (26049 hom., cov: 26)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• 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: 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

Specifications for PIK3CA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 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.-76-3532C>A		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.-76-3532C>A		intron	N/A	ENSP00000263967.3	P42336
	PIK3CA	ENST00000955190.1		c.-76-3532C>A		intron	N/A	ENSP00000625249.1
	PIK3CA	ENST00000876545.1		c.-76-3532C>A		intron	N/A	ENSP00000546604.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 86404 AN: 150562 Hom.: 26012 Cov.: 26

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.574 AC: 86498 AN: 150682 Hom.: 26049 Cov.: 26 AF XY: 0.565 AC XY: 41552 AN XY: 73548

African (AFR) AF: 0.761 AC: 31212 AN: 41010

American (AMR) AF: 0.510 AC: 7715 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1975 AN: 3456

East Asian (EAS) AF: 0.225 AC: 1146 AN: 5100

South Asian (SAS) AF: 0.466 AC: 2208 AN: 4738

European-Finnish (FIN) AF: 0.435 AC: 4461 AN: 10264

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

European-Non Finnish (NFE) AF: 0.527 AC: 35697 AN: 67708

Other (OTH) AF: 0.587 AC: 1212 AN: 2066

Alfa AF: 0.540 Hom.: 42283

Bravo AF: 0.589

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.73
PhyloP100		-0.48
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: rs870995; hg19: chr3-178913006;