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GeneBe

15-41990170-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001395548.1(PLA2G4E):c.1449C>T(p.Ile483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,768 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 34 hom. )

Consequence

PLA2G4E
NM_001395548.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.27
Variant links:
Genes affected
PLA2G4E (HGNC:24791): (phospholipase A2 group IVE) This gene encodes a member of the cytosolic phospholipase A2 group IV family. Members of this family are involved in regulation of membrane tubule-mediated transport. The enzyme encoded by this member of the family plays a role in trafficking through the clathrin-independent endocytic pathway. The enzyme regulates the recycling process via formation of tubules that transport internalized clathrin-independent cargo proteins back to the cell surface. [provided by RefSeq, Jan 2017]
PLA2G4E-AS1 (HGNC:51419): (PLA2G4E antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

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=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-41990170-G-A is Benign according to our data. Variant chr15-41990170-G-A is described in ClinVar as [Benign]. Clinvar id is 785484.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.27 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1856/152308) while in subpopulation AFR AF= 0.0425 (1764/41542). AF 95% confidence interval is 0.0408. There are 42 homozygotes in gnomad4. There are 867 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLA2G4ENM_001395548.1 linkuse as main transcriptc.1449C>T p.Ile483= synonymous_variant 14/20 ENST00000696112.1
PLA2G4E-AS1NR_120334.1 linkuse as main transcriptn.544-6969G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLA2G4EENST00000696112.1 linkuse as main transcriptc.1449C>T p.Ile483= synonymous_variant 14/20 NM_001395548.1 A2
PLA2G4E-AS1ENST00000499478.2 linkuse as main transcriptn.544-6969G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0122
AC:
1850
AN:
152190
Hom.:
42
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0424
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00288
AC:
718
AN:
249140
Hom.:
13
AF XY:
0.00207
AC XY:
280
AN XY:
135154
show subpopulations
Gnomad AFR exome
AF:
0.0427
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000443
Gnomad OTH exome
AF:
0.00116
GnomAD4 exome
AF:
0.00118
AC:
1722
AN:
1461460
Hom.:
34
Cov.:
31
AF XY:
0.00101
AC XY:
732
AN XY:
727022
show subpopulations
Gnomad4 AFR exome
AF:
0.0444
Gnomad4 AMR exome
AF:
0.00145
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.00252
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0122
AC:
1856
AN:
152308
Hom.:
42
Cov.:
32
AF XY:
0.0116
AC XY:
867
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0425
Gnomad4 AMR
AF:
0.00418
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00652
Hom.:
11
Bravo
AF:
0.0137
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
13
Dann
Benign
0.85

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

LitVar

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

Other links and lift over

dbSNP: rs74010937; hg19: chr15-42282368; API