Genetic Variant PLA2G4A:c.-70+10176G>T (chr1-186839211-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.-70+10176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,052 control chromosomes in the GnomAD database, including 10,228 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 0.36 ( 10228 hom., cov: 32)

Consequence

PLA2G4A
NM_024420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3 link	c.-70+10176G>T	intron_variant	Intron 1 of 17	ENST00000367466.4	NP_077734.2	P47712
PLA2G4A	NM_001311193.2 link	c.-70+10176G>T	intron_variant	Intron 1 of 15		NP_001298122.2	P47712B4DZI4
PLA2G4A	XM_011509642.3 link	c.-70+10161G>T	intron_variant	Intron 1 of 17		XP_011507944.1	P47712
PLA2G4A	XM_047422599.1 link	c.-70+10176G>T	intron_variant	Intron 1 of 14		XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4 link	c.-70+10176G>T		intron_variant	Intron 1 of 17	1	NM_024420.3	ENSP00000356436.3		P47712

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55050

AN:

151934

Hom.:

10227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.403

Gnomad EAS

AF:

0.579

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.363

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

GnomAD4 genome

AF:

0.362

AC:

55078

AN:

152052

Hom.:

10228

Cov.:

AF XY:

0.368

AC XY:

27332

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.370

AC:

15363

AN:

41468

American (AMR)

AF:

0.401

AC:

6131

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

1399

AN:

3470

East Asian (EAS)

AF:

0.578

AC:

2980

AN:

5152

South Asian (SAS)

AF:

0.311

AC:

1503

AN:

4826

European-Finnish (FIN)

AF:

0.379

AC:

4007

AN:

10562

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22518

AN:

67966

Other (OTH)

AF:

0.360

AC:

762

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1789

3578

5368

7157

8946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.344

Hom.:

17050

Bravo

AF:

0.368

Asia WGS

AF:

0.413

AC:

1434

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.75

(source)

DANN

Benign

0.71

PhyloP100

-0.060

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