rs1607237

Variant names:

• chr3-179232509-C-T
• rs1607237
• NM_006218.4:c.2937-1585C>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.2937-1585C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,014 control chromosomes in the GnomAD database, including 36,154 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 0.67 (36154 hom., cov: 32)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 30 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 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.2937-1585C>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.2937-1585C>T		intron	N/A	ENSP00000263967.3	P42336
	PIK3CA	ENST00000955190.1		c.2967-1585C>T		intron	N/A	ENSP00000625249.1
	PIK3CA	ENST00000876545.1		c.2937-1585C>T		intron	N/A	ENSP00000546604.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101503 AN: 151896 Hom.: 36100 Cov.: 32

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.668 AC: 101613 AN: 152014 Hom.: 36154 Cov.: 32 AF XY: 0.659 AC XY: 48933 AN XY: 74272

African (AFR) AF: 0.913 AC: 37929 AN: 41524

American (AMR) AF: 0.572 AC: 8733 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2220 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5160

South Asian (SAS) AF: 0.619 AC: 2982 AN: 4820

European-Finnish (FIN) AF: 0.486 AC: 5117 AN: 10520

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40745 AN: 67946

Other (OTH) AF: 0.672 AC: 1416 AN: 2108

Alfa AF: 0.620 Hom.: 122910

Bravo AF: 0.685

Asia WGS AF: 0.469 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.53
DANN	Benign	0.38
PhyloP100		-0.63
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1607237;

hg19: chr3-178950297;