Genetic Variant PLA2G4C:c.257+1183C>A (chr19-48103405-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_003706.3(PLA2G4C):c.257+1183C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,246 control chromosomes in the GnomAD database, including 11,355 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 0.32 ( 11347 hom., cov: 31)

Exomes 𝑓: 0.19 ( 8 hom. )

Consequence

PLA2G4C
NM_003706.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.635

Publications

4 publications found

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]

PLA2G4C 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=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003706.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLA2G4C	NM_003706.3	MANE Select	c.257+1183C>A	intron	N/A	NP_003697.2	Q9UP65-1
PLA2G4C	NM_001159322.2		c.287+1183C>A	intron	N/A	NP_001152794.1	Q9UP65-3
PLA2G4C	NM_001159323.2		c.257+1183C>A	intron	N/A	NP_001152795.1	Q9UP65-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLA2G4C	ENST00000599921.6	TSL:1 MANE Select	c.257+1183C>A	intron	N/A	ENSP00000469473.1	Q9UP65-1
PLA2G4C	ENST00000599063.5	TSL:1	n.570+1183C>A	intron	N/A
PLA2G4C	ENST00000887096.1		c.257+1183C>A	intron	N/A	ENSP00000557155.1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48442

AN:

151844

Hom.:

11316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.190

AC:

AN:

284

Hom.:

Cov.:

AF XY:

0.212

AC XY:

AN XY:

212

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.143

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.178

AC:

AN:

202

Other (OTH)

AF:

0.227

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.319

AC:

48518

AN:

151962

Hom.:

11347

Cov.:

AF XY:

0.315

AC XY:

23374

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.664

AC:

27471

AN:

41384

American (AMR)

AF:

0.225

AC:

3436

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3464

East Asian (EAS)

AF:

0.381

AC:

1969

AN:

5164

South Asian (SAS)

AF:

0.218

AC:

1053

AN:

4820

European-Finnish (FIN)

AF:

0.162

AC:

1709

AN:

10572

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11595

AN:

67986

Other (OTH)

AF:

0.279

AC:

590

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1328

2656

3984

5312

6640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.220

Hom.:

2951

Bravo

AF:

0.341

Asia WGS

AF:

0.317

AC:

1102

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.0

(source)

DANN

Benign

0.45

PhyloP100

-0.64

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over