Genetic Variant PLA2G7:p.Ile198Thr (chr6-46711566-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005084.4(PLA2G7):c.593T>C(p.Ile198Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,464 control chromosomes in the GnomAD database, including 4,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.10 ( 1216 hom., cov: 32)

Exomes 𝑓: 0.059 ( 3637 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:2

Conservation

PhyloP100: -1.09

Publications

71 publications found

Variant links:

Genes affected

PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]

PLA2G7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018128157).

BP6

Variant 6-46711566-A-G is Benign according to our data. Variant chr6-46711566-A-G is described in ClinVar as Benign. ClinVar VariationId is 7915.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4 link	c.593T>C	p.Ile198Thr	missense_variant	Exon 7 of 12	ENST00000274793.12	NP_005075.3	Q13093

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12 link	c.593T>C	p.Ile198Thr	missense_variant	Exon 7 of 12	1	NM_005084.4	ENSP00000274793.7		Q13093
PLA2G7	ENST00000537365.1 link	c.593T>C	p.Ile198Thr	missense_variant	Exon 7 of 12	1		ENSP00000445666.1		Q13093

Frequencies

GnomAD3 genomes

AF:

0.0994

AC:

15116

AN:

152020

Hom.:

1210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0472

Gnomad OTH

AF:

0.0894

GnomAD2 exomes

AF:

0.0680

AC:

17097

AN:

251296

AF XY:

0.0680

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.0379

Gnomad ASJ exome

AF:

0.0701

Gnomad EAS exome

AF:

0.0960

Gnomad FIN exome

AF:

0.0297

Gnomad NFE exome

AF:

0.0468

Gnomad OTH exome

AF:

0.0653

GnomAD4 exome

AF:

0.0590

AC:

86253

AN:

1461326

Hom.:

3637

Cov.:

AF XY:

0.0600

AC XY:

43614

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.226

AC:

7578

AN:

33460

American (AMR)

AF:

0.0402

AC:

1799

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0680

AC:

1777

AN:

26118

East Asian (EAS)

AF:

0.161

AC:

6379

AN:

39676

South Asian (SAS)

AF:

0.108

AC:

9274

AN:

86244

European-Finnish (FIN)

AF:

0.0325

AC:

1736

AN:

53416

Middle Eastern (MID)

AF:

0.0935

AC:

539

AN:

5764

European-Non Finnish (NFE)

AF:

0.0476

AC:

52956

AN:

1111550

Other (OTH)

AF:

0.0698

AC:

4215

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4120

8241

12361

16482

20602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2190

4380

6570

8760

10950

<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:

0.0995

AC:

15138

AN:

152138

Hom.:

1216

Cov.:

AF XY:

0.0994

AC XY:

7392

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.220

AC:

9143

AN:

41470

American (AMR)

AF:

0.0569

AC:

870

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3472

East Asian (EAS)

AF:

0.113

AC:

584

AN:

5178

South Asian (SAS)

AF:

0.112

AC:

540

AN:

4820

European-Finnish (FIN)

AF:

0.0312

AC:

331

AN:

10606

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0472

AC:

3208

AN:

67996

Other (OTH)

AF:

0.0903

AC:

191

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

649

1299

1948

2598

3247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.0649

Hom.:

2431

Bravo

AF:

0.104

TwinsUK

AF:

0.0429

AC:

159

ALSPAC

AF:

0.0418

AC:

161

ESP6500AA

AF:

0.213

AC:

940

ESP6500EA

AF:

0.0509

AC:

438

ExAC

AF:

0.0731

AC:

8871

Asia WGS

AF:

0.135

AC:

470

AN:

3478

EpiCase

AF:

0.0515

EpiControl

AF:

0.0512

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RECLASSIFIED - MYOC POLYMORPHISM

Benign:1

May 01, 2000

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

PLA2G7-related disorder

Benign:1

Dec 23, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.017

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.31

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

N;N

PhyloP100

-1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.016

Sift

Benign

0.65

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;B

Vest4

0.031

MPC

0.0044

ClinPred

0.0028

GERP RS

-7.6

Varity_R

0.15

gMVP

0.29

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over