6-46705206-A-G

Position:

chr6-46705206-A-G

Variant summary

Our verdict is Benign. Variant got -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. 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

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 made for transcript

Verdict is Benign. Variant got -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. Variant chr6-46705206-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein
PLA2G7	NM_005084.4 linkuse as main transcript	c.1136T>C	p.Val379Ala	missense_variant	11/12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2 linkuse as main transcript	c.1136T>C	p.Val379Ala	missense_variant	11/12		NP_001161829.1
PLA2G7	XM_005249408.5 linkuse as main transcript	c.1136T>C	p.Val379Ala	missense_variant	11/12		XP_005249465.1
PLA2G7	XM_047419359.1 linkuse as main transcript	c.1001T>C	p.Val334Ala	missense_variant	10/11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12 linkuse as main transcript	c.1136T>C	p.Val379Ala	missense_variant	11/12	1	NM_005084.4	ENSP00000274793	P1
PLA2G7	ENST00000537365.1 linkuse as main transcript	c.1136T>C	p.Val379Ala	missense_variant	11/12	1		ENSP00000445666	P1

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

GnomAD3 exomes

AF:

0.805

AC:

201897

AN:

250760

Hom.:

81426

AF XY:

0.805

AC XY:

109043

AN XY:

135520

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 SAS exome

AF:

0.839

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

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.835

Gnomad4 ASJ exome

AF:

0.800

Gnomad4 EAS exome

AF:

0.886

Gnomad4 SAS exome

AF:

0.839

Gnomad4 FIN exome

AF:

0.755

Gnomad4 NFE exome

AF:

0.804

Gnomad4 OTH exome

AF:

0.805

GnomAD4 genome

AF:

0.791

AC:

120284

AN:

152130

Hom.:

47651

Cov.:

AF XY:

0.791

AC XY:

58813

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.754

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.793

Gnomad4 EAS

AF:

0.886

Gnomad4 SAS

AF:

0.854

Gnomad4 FIN

AF:

0.760

Gnomad4 NFE

AF:

0.801

Gnomad4 OTH

AF:

0.798

Alfa

AF:

0.797

Hom.:

85786

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2018	This variant is associated with the following publications: (PMID: 24463064, 24682749, 10733466, 20926117, 21880383, 19763134, 12801611) -
not provided, no classification provided	literature only	Lab. of Molecular Biology of Arterial Hypertension University of Padova	-	- -

RECLASSIFIED - POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 2004

- -

PLA2G7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

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

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

MutationTaster

Benign

1.0

P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over