Genetic Variant PLA2G7:p.Arg92His (chr6-46716485-C-T) – 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.275G>A(p.Arg92His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,612,368 control chromosomes in the GnomAD database, including 65,276 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 0.28 ( 6251 hom., cov: 32)

Exomes 𝑓: 0.28 ( 59025 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: -2.83

Publications

114 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=5.055892E-5).

BP6

Variant 6-46716485-C-T is Benign according to our data. Variant chr6-46716485-C-T is described in ClinVar as Benign. ClinVar VariationId is 56163.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005084.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	NM_005084.4	MANE Select	c.275G>A	p.Arg92His	missense	Exon 4 of 12	NP_005075.3
	PLA2G7	NM_001168357.2		c.275G>A	p.Arg92His	missense	Exon 4 of 12	NP_001161829.1	Q13093

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLA2G7	ENST00000274793.12	TSL:1 MANE Select	c.275G>A	p.Arg92His	missense	Exon 4 of 12	ENSP00000274793.7	Q13093
PLA2G7	ENST00000537365.1	TSL:1	c.275G>A	p.Arg92His	missense	Exon 4 of 12	ENSP00000445666.1	Q13093
PLA2G7	ENST00000878321.1		c.275G>A	p.Arg92His	missense	Exon 4 of 12	ENSP00000548380.1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42968

AN:

151864

Hom.:

6253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.308

AC:

77285

AN:

251194

AF XY:

0.313

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.276

AC:

402482

AN:

1460386

Hom.:

59025

Cov.:

AF XY:

0.282

AC XY:

205112

AN XY:

726582

show subpopulations

African (AFR)

AF:

0.282

AC:

9441

AN:

33452

American (AMR)

AF:

0.373

AC:

16671

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

9056

AN:

26126

East Asian (EAS)

AF:

0.204

AC:

8093

AN:

39674

South Asian (SAS)

AF:

0.503

AC:

43355

AN:

86214

European-Finnish (FIN)

AF:

0.270

AC:

14402

AN:

53406

Middle Eastern (MID)

AF:

0.356

AC:

2050

AN:

5754

European-Non Finnish (NFE)

AF:

0.254

AC:

282336

AN:

1110702

Other (OTH)

AF:

0.283

AC:

17078

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

14248

28496

42743

56991

71239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9738

19476

29214

38952

48690

<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:

0.283

AC:

43002

AN:

151982

Hom.:

6251

Cov.:

AF XY:

0.287

AC XY:

21331

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.281

AC:

11641

AN:

41452

American (AMR)

AF:

0.340

AC:

5195

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1153

AN:

3470

East Asian (EAS)

AF:

0.206

AC:

1062

AN:

5156

South Asian (SAS)

AF:

0.514

AC:

2467

AN:

4804

European-Finnish (FIN)

AF:

0.287

AC:

3023

AN:

10546

Middle Eastern (MID)

AF:

0.325

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.257

AC:

17477

AN:

67962

Other (OTH)

AF:

0.299

AC:

630

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1579

3158

4738

6317

7896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.266

Hom.:

24142

Bravo

AF:

0.279

TwinsUK

AF:

0.255

AC:

947

ALSPAC

AF:

0.257

AC:

989

ESP6500AA

AF:

0.276

AC:

1216

ESP6500EA

AF:

0.262

AC:

2250

ExAC

AF:

0.303

AC:

36807

Asia WGS

AF:

0.375

AC:

1303

AN:

3478

EpiCase

AF:

0.268

EpiControl

AF:

0.262

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PLA2G7-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.041

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.059

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.16

MetaRNN

Benign

0.000051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.51

PhyloP100

-2.8

PrimateAI

Benign

0.20

PROVEAN

Benign

0.61

REVEL

Benign

0.057

Sift

Benign

0.59

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.062

MPC

0.0045

ClinPred

0.017

GERP RS

-10

Varity_R

0.30

gMVP

0.53

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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