6-46705206-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005084.4(PLA2G7):c.1136T>C(p.Val379Ala) variant causes a missense change. The variant allele was found at a frequency of 0.805 in 1,606,512 control chromosomes in the GnomAD database, including 520,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.79 ( 47651 hom., cov: 33)

Exomes 𝑓: 0.81 ( 473060 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3O:1

Conservation

PhyloP100: 6.99

Publications

130 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.410112E-6).

BP6

Variant 6-46705206-A-G is Benign according to our data. Variant chr6-46705206-A-G is described in ClinVar as [Benign]. Clinvar id is 7916.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4 link	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12	ENST00000274793.12	NP_005075.3	Q13093
PLA2G7	NM_001168357.2 link	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12		NP_001161829.1	Q13093
PLA2G7	XM_005249408.5 link	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12		XP_005249465.1	Q13093
PLA2G7	XM_047419359.1 link	c.1001T>C	p.Val334Ala	missense_variant	Exon 10 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12 link	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12	1	NM_005084.4	ENSP00000274793.7		Q13093
PLA2G7	ENST00000537365.1 link	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12	1		ENSP00000445666.1		Q13093

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

120206

AN:

152012

Hom.:

47626

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.822

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.854

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.796

Gnomad NFE

AF:

0.801

Gnomad OTH

AF:

0.797

GnomAD2 exomes

AF:

0.805

AC:

201897

AN:

250760

AF XY:

0.805

show subpopulations

Gnomad AFR exome

AF:

0.747

Gnomad AMR exome

AF:

0.838

Gnomad ASJ exome

AF:

0.794

Gnomad EAS exome

AF:

0.873

Gnomad FIN exome

AF:

0.756

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.790

GnomAD4 exome

AF:

0.806

AC:

1172329

AN:

1454382

Hom.:

473060

Cov.:

AF XY:

0.807

AC XY:

584403

AN XY:

724066

show subpopulations

African (AFR)

AF:

0.750

AC:

24976

AN:

33312

American (AMR)

AF:

0.835

AC:

37276

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.800

AC:

20856

AN:

26078

East Asian (EAS)

AF:

0.886

AC:

35129

AN:

39628

South Asian (SAS)

AF:

0.839

AC:

72204

AN:

86102

European-Finnish (FIN)

AF:

0.755

AC:

40244

AN:

53304

Middle Eastern (MID)

AF:

0.821

AC:

4710

AN:

5738

European-Non Finnish (NFE)

AF:

0.804

AC:

888540

AN:

1105444

Other (OTH)

AF:

0.805

AC:

48394

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10909

21818

32727

43636

54545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.791

AC:

120284

AN:

152130

Hom.:

47651

Cov.:

AF XY:

0.791

AC XY:

58813

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.754

AC:

31297

AN:

41492

American (AMR)

AF:

0.823

AC:

12564

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.793

AC:

2752

AN:

3470

East Asian (EAS)

AF:

0.886

AC:

4587

AN:

5180

South Asian (SAS)

AF:

0.854

AC:

4127

AN:

4830

European-Finnish (FIN)

AF:

0.760

AC:

8050

AN:

10590

Middle Eastern (MID)

AF:

0.798

AC:

233

AN:

292

European-Non Finnish (NFE)

AF:

0.801

AC:

54432

AN:

67992

Other (OTH)

AF:

0.798

AC:

1683

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1311

2622

3933

5244

6555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.798

Hom.:

170027

Bravo

AF:

0.787

TwinsUK

AF:

0.809

AC:

3000

ALSPAC

AF:

0.799

AC:

3081

ESP6500AA

AF:

0.748

AC:

3294

ESP6500EA

AF:

0.804

AC:

6914

ExAC

AF:

0.803

AC:

97465

Asia WGS

AF:

0.864

AC:

3000

AN:

3476

EpiCase

AF:

0.792

EpiControl

AF:

0.793

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Lab. of Molecular Biology of Arterial Hypertension University of Padova

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Dec 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24463064, 24682749, 10733466, 20926117, 21880383, 19763134, 12801611) -

RECLASSIFIED - MYOC POLYMORPHISM

Benign:1

Jul 01, 2004

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

PLA2G7-related disorder

Benign:1

Sep 24, 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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.50

.;T

MetaRNN

Benign

0.0000094

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

7.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.20

Sift

Benign

0.32

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.99

D;D

Vest4

0.29

MPC

0.019

ClinPred

0.043

GERP RS

5.9

Varity_R

0.48

gMVP

0.42

Mutation Taster

=98/2

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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6-46705206-A-G

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