dbSNP rs12746200: PLA2G4A:c.115+9538A>G (chr1-186880054-A-G) – 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.115+9538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,010 control chromosomes in the GnomAD database, including 577 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 0.075 ( 577 hom., cov: 32)

Consequence

PLA2G4A
NM_024420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.430

Publications

17 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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3 link	c.115+9538A>G		intron_variant	Intron 3 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.115+9538A>G		intron_variant	Intron 3 of 17	1	NM_024420.3	ENSP00000356436.3		P47712
PLA2G4A	ENST00000466600.1 link	n.184+9538A>G		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11343

AN:

151892

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0641

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.0737

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0945

Gnomad OTH

AF:

0.113

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

GnomAD4 genome

AF:

0.0747

AC:

11349

AN:

152010

Hom.:

577

Cov.:

AF XY:

0.0738

AC XY:

5485

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0175

AC:

727

AN:

41526

American (AMR)

AF:

0.126

AC:

1912

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

438

AN:

3466

East Asian (EAS)

AF:

0.0645

AC:

333

AN:

5164

South Asian (SAS)

AF:

0.0654

AC:

315

AN:

4820

European-Finnish (FIN)

AF:

0.0737

AC:

781

AN:

10596

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0945

AC:

6419

AN:

67926

Other (OTH)

AF:

0.111

AC:

235

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

527

1054

1582

2109

2636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0855

Hom.:

1597

Bravo

AF:

0.0762

Asia WGS

AF:

0.0620

AC:

214

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.0

(source)

DANN

Benign

0.82

PhyloP100

0.43

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

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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