Variant 6-46711566-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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 -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 id 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/exons	MANE	UniProt
PLA2G7	NM_005084.4 linkuse as main transcript	c.593T>C	p.Ile198Thr	missense_variant	7/12	ENST00000274793.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G7	ENST00000274793.12 linkuse as main transcript	c.593T>C	p.Ile198Thr	missense_variant	7/12	1	NM_005084.4	P1
PLA2G7	ENST00000537365.1 linkuse as main transcript	c.593T>C	p.Ile198Thr	missense_variant	7/12	1		P1

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

GnomAD3 exomes

AF:

0.0680

AC:

17097

AN:

251296

Hom.:

873

AF XY:

0.0680

AC XY:

9233

AN XY:

135806

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 SAS exome

AF:

0.109

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

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0402

Gnomad4 ASJ exome

AF:

0.0680

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0476

Gnomad4 OTH exome

AF:

0.0698

GnomAD4 genome

AF:

0.0995

AC:

15138

AN:

152138

Hom.:

1216

Cov.:

AF XY:

0.0994

AC XY:

7392

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0569

Gnomad4 ASJ

AF:

0.0706

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.0472

Gnomad4 OTH

AF:

0.0903

Alfa

AF:

0.0598

Hom.:

984

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 - POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 01, 2000

- -

PLA2G7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 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

0.051

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.017

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

MutationTaster

Benign

1.0

P;P;P;P

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

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

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