dbSNP rs12720541: PLA2G4A:c.379-6025G>T (chr1-186900940-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024420.3(PLA2G4A):c.379-6025G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,028 control chromosomes in the GnomAD database, including 5,750 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 0.27 ( 5750 hom., cov: 32)

Consequence

PLA2G4A
NM_024420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0180

Publications

9 publications found

Variant links:

Genes affected

PLA2G4A (HGNC:9035): (phospholipase A2 group IVA) This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

PLA2G4A Gene-Disease associations (from GenCC):

cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics
cryptogenic multifocal ulcerous stenosing enteritis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PLA2G4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3 link	c.379-6025G>T		intron_variant	Intron 5 of 17	ENST00000367466.4	NP_077734.2	P47712

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4 link	c.379-6025G>T		intron_variant	Intron 5 of 17	1	NM_024420.3	ENSP00000356436.3		P47712
PLA2G4A	ENST00000466600.1 link	n.448-6025G>T		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40293

AN:

151910

Hom.:

5741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.279

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

GnomAD4 genome

AF:

0.265

AC:

40332

AN:

152028

Hom.:

5750

Cov.:

AF XY:

0.267

AC XY:

19852

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.216

AC:

8981

AN:

41488

American (AMR)

AF:

0.405

AC:

6183

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

690

AN:

3468

East Asian (EAS)

AF:

0.162

AC:

834

AN:

5164

South Asian (SAS)

AF:

0.340

AC:

1640

AN:

4826

European-Finnish (FIN)

AF:

0.261

AC:

2751

AN:

10554

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18364

AN:

67962

Other (OTH)

AF:

0.278

AC:

587

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.273

Hom.:

2800

Bravo

AF:

0.276

Asia WGS

AF:

0.268

AC:

934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

(source)

DANN

Benign

0.59

PhyloP100

0.018

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over