Genetic Variant PLA2G4A:c.33+7045C>T (chr1-186861432-C-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.33+7045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,220 control chromosomes in the GnomAD database, including 56,904 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 0.86 ( 56904 hom., cov: 32)

Consequence

PLA2G4A
NM_024420.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Publications

5 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PLA2G4A	NM_024420.3 link	c.33+7045C>T	intron_variant	Intron 2 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2 link	c.33+7045C>T	intron_variant	Intron 2 of 15		NP_001298122.2
PLA2G4A	XM_011509642.3 link	c.33+7045C>T	intron_variant	Intron 2 of 17		XP_011507944.1
PLA2G4A	XM_047422599.1 link	c.33+7045C>T	intron_variant	Intron 2 of 14		XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4 link	c.33+7045C>T		intron_variant	Intron 2 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1 link	n.102+7045C>T		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131064

AN:

152102

Hom.:

56840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.963

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.834

Gnomad FIN

AF:

0.780

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.823

Gnomad OTH

AF:

0.858

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

GnomAD4 genome

AF:

0.862

AC:

131188

AN:

152220

Hom.:

56904

Cov.:

AF XY:

0.860

AC XY:

63994

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.963

AC:

40020

AN:

41568

American (AMR)

AF:

0.866

AC:

13237

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

2916

AN:

3472

East Asian (EAS)

AF:

0.788

AC:

4075

AN:

5174

South Asian (SAS)

AF:

0.835

AC:

4030

AN:

4828

European-Finnish (FIN)

AF:

0.780

AC:

8255

AN:

10586

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.823

AC:

55947

AN:

67992

Other (OTH)

AF:

0.859

AC:

1818

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

908

1816

2723

3631

4539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.833

Hom.:

37820

Bravo

AF:

0.871

Asia WGS

AF:

0.827

AC:

2871

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.63

(source)

DANN

Benign

0.24

PhyloP100

-0.51

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