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GeneBe

19-48074825-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003706.3(PLA2G4C):c.948T>C(p.Asn316=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,612,898 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 54 hom., cov: 31)
Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

PLA2G4C
NM_003706.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34
Variant links:
Genes affected
PLA2G4C (HGNC:9037): (phospholipase A2 group IVC) This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.94).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-48074825-A-G is Benign according to our data. Variant chr19-48074825-A-G is described in ClinVar as [Benign]. Clinvar id is 788028.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=-1.34 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 = 0.0134 (2040/152120) while in subpopulation AFR AF= 0.0466 (1931/41478). AF 95% confidence interval is 0.0448. There are 54 homozygotes in gnomad4. There are 985 alleles in male gnomad4 subpopulation. Median coverage is 31. 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 53 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLA2G4CNM_003706.3 linkuse as main transcriptc.948T>C p.Asn316= synonymous_variant 12/17 ENST00000599921.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLA2G4CENST00000599921.6 linkuse as main transcriptc.948T>C p.Asn316= synonymous_variant 12/171 NM_003706.3 A2Q9UP65-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0134
AC:
2031
AN:
152002
Hom.:
53
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0465
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00505
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00910
GnomAD3 exomes
AF:
0.00384
AC:
961
AN:
250102
Hom.:
19
AF XY:
0.00297
AC XY:
401
AN XY:
135170
show subpopulations
Gnomad AFR exome
AF:
0.0495
Gnomad AMR exome
AF:
0.00349
Gnomad ASJ exome
AF:
0.000805
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000230
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.000987
GnomAD4 exome
AF:
0.00140
AC:
2048
AN:
1460778
Hom.:
41
Cov.:
30
AF XY:
0.00123
AC XY:
892
AN XY:
726678
show subpopulations
Gnomad4 AFR exome
AF:
0.0464
Gnomad4 AMR exome
AF:
0.00343
Gnomad4 ASJ exome
AF:
0.000576
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000648
Gnomad4 OTH exome
AF:
0.00389
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0134
AC:
2040
AN:
152120
Hom.:
54
Cov.:
31
AF XY:
0.0132
AC XY:
985
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0466
Gnomad4 AMR
AF:
0.00505
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00506
Hom.:
10
Bravo
AF:
0.0153
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
0.89
Dann
Benign
0.47

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: rs3218742; hg19: chr19-48578082; API