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GeneBe

1-186870523-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024420.3(PLA2G4A):c.115+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,591,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

PLA2G4A
NM_024420.3 splice_region, intron

Scores

2
Splicing: ADA: 0.00001923
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.831
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-186870523-G-A is Benign according to our data. Variant chr1-186870523-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2046836.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLA2G4ANM_024420.3 linkuse as main transcriptc.115+7G>A splice_region_variant, intron_variant ENST00000367466.4
PLA2G4ANM_001311193.2 linkuse as main transcriptc.115+7G>A splice_region_variant, intron_variant
PLA2G4AXM_011509642.3 linkuse as main transcriptc.115+7G>A splice_region_variant, intron_variant
PLA2G4AXM_047422599.1 linkuse as main transcriptc.115+7G>A splice_region_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLA2G4AENST00000367466.4 linkuse as main transcriptc.115+7G>A splice_region_variant, intron_variant 1 NM_024420.3 P1
PLA2G4AENST00000466600.1 linkuse as main transcriptn.184+7G>A splice_region_variant, intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000197
AC:
30
AN:
152034
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000967
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000272
AC:
68
AN:
249906
Hom.:
0
AF XY:
0.000326
AC XY:
44
AN XY:
135008
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000299
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000824
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000336
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000222
AC:
320
AN:
1439118
Hom.:
0
Cov.:
27
AF XY:
0.000248
AC XY:
178
AN XY:
717170
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000616
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000794
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000194
Gnomad4 OTH exome
AF:
0.000252
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000197
AC:
30
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0000964
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000306
Hom.:
0
Bravo
AF:
0.000189
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.0000594

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 26, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
Cadd
Benign
0.082
Dann
Benign
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000019
dbscSNV1_RF
Benign
0.022
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs182035463; hg19: chr1-186839655; API