Genetic Variant NM_003706.3:c.1257+48C>T (chr19-48061950-G-A) – 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.1257+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,589,648 control chromosomes in the GnomAD database, including 1,419 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 0.055 ( 342 hom., cov: 31)

Exomes 𝑓: 0.034 ( 1077 hom. )

Consequence

PLA2G4C
NM_003706.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.512

Publications

6 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:

PLA2G4C-AS1 (HGNC:51585): (PLA2G4C antisense RNA 1)

PLA2G4C-AS1 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4C	NM_003706.3 link	c.1257+48C>T		intron_variant	Intron 14 of 16	ENST00000599921.6	NP_003697.2	Q9UP65-1A0A024QZH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4C	ENST00000599921.6 link	c.1257+48C>T		intron_variant	Intron 14 of 16	1	NM_003706.3	ENSP00000469473.1		Q9UP65-1
PLA2G4C	ENST00000595161.5 link	c.321+48C>T		intron_variant	Intron 3 of 4	3		ENSP00000469528.1		M0QY18

Frequencies

GnomAD3 genomes

AF:

0.0553

AC:

8398

AN:

151976

Hom.:

343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0569

GnomAD2 exomes

AF:

0.0329

AC:

7987

AN:

242532

AF XY:

0.0314

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0259

Gnomad ASJ exome

AF:

0.0418

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0352

Gnomad OTH exome

AF:

0.0419

GnomAD4 exome

AF:

0.0342

AC:

49167

AN:

1437554

Hom.:

1077

Cov.:

AF XY:

0.0334

AC XY:

23917

AN XY:

715850

show subpopulations

African (AFR)

AF:

0.124

AC:

4037

AN:

32582

American (AMR)

AF:

0.0291

AC:

1269

AN:

43680

Ashkenazi Jewish (ASJ)

AF:

0.0422

AC:

1088

AN:

25752

East Asian (EAS)

AF:

0.00

AC:

AN:

38822

South Asian (SAS)

AF:

0.0141

AC:

1202

AN:

85350

European-Finnish (FIN)

AF:

0.0135

AC:

700

AN:

51790

Middle Eastern (MID)

AF:

0.0582

AC:

323

AN:

5552

European-Non Finnish (NFE)

AF:

0.0349

AC:

38214

AN:

1094566

Other (OTH)

AF:

0.0393

AC:

2334

AN:

59460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2240

4479

6719

8958

11198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1476

2952

4428

5904

7380

<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:

0.0553

AC:

8408

AN:

152094

Hom.:

342

Cov.:

AF XY:

0.0532

AC XY:

3957

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.116

AC:

4794

AN:

41454

American (AMR)

AF:

0.0447

AC:

682

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0114

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0142

AC:

150

AN:

10594

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0352

AC:

2390

AN:

67988

Other (OTH)

AF:

0.0563

AC:

119

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

414

828

1243

1657

2071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0380

Hom.:

219

Bravo

AF:

0.0626

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

(source)

DANN

Benign

0.90

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over