rs141178472

Variant names:

• chr3-179234393-T-C
• rs141178472
• NM_006218.4:c.*29T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-179234393-T-C
• chr3-179234393-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006218.4(PIK3CA):​c.*29T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,575,996 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (38 hom.)
• Consequence: PIK3CA NM_006218.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.938
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-179234393-T-C is Benign according to our data. Variant chr3-179234393-T-C is described in ClinVar as Benign. ClinVar VariationId is 246606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00318 (484/152234) while in subpopulation NFE AF = 0.00597 (406/67994). AF 95% confidence interval is 0.00549. There are 0 homozygotes in GnomAd4. There are 201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 484 AD gene.

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.*29T>C		3_prime_UTR	Exon 21 of 21	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.*29T>C		3_prime_UTR	Exon 21 of 21	ENSP00000263967.3	P42336
	PIK3CA	ENST00000955190.1		c.*29T>C		3_prime_UTR	Exon 21 of 21	ENSP00000625249.1
	PIK3CA	ENST00000876545.1		c.*29T>C		3_prime_UTR	Exon 22 of 22	ENSP00000546604.1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 484 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00597

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00303 AC: 679 AN: 224024 AF XY: 0.00314

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000165

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.00632 AC: 9005 AN: 1423762 Hom.: 38 Cov.: 28 AF XY: 0.00606 AC XY: 4269 AN XY: 704394

African (AFR) AF: 0.00104 AC: 34 AN: 32604

American (AMR) AF: 0.00162 AC: 69 AN: 42612

Ashkenazi Jewish (ASJ) AF: 0.0000413 AC: 1 AN: 24216

East Asian (EAS) AF: 0.00 AC: 0 AN: 39240

South Asian (SAS) AF: 0.000137 AC: 11 AN: 80582

European-Finnish (FIN) AF: 0.000457 AC: 23 AN: 50332

Middle Eastern (MID) AF: 0.000358 AC: 2 AN: 5584

European-Non Finnish (NFE) AF: 0.00787 AC: 8573 AN: 1089752

Other (OTH) AF: 0.00496 AC: 292 AN: 58840

GnomAD4 genome AF: 0.00318 AC: 484 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74432

African (AFR) AF: 0.00120 AC: 50 AN: 41564

American (AMR) AF: 0.00105 AC: 16 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00597 AC: 406 AN: 67994

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00352 Hom.: 0

Bravo AF: 0.00357

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cowden syndrome (1)
-	-	1	not provided (1)
-	-	1	PIK3CA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.8
DANN	Benign	0.86
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism

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: rs141178472; hg19: chr3-178952181; COSMIC: COSV55915946; COSMIC: COSV55915946;