6-46705206-A-G

Variant names:

• chr6-46705206-A-G
• rs1051931
• NM_005084.4:c.1136T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:3 O:1
• Conservation: PhyloP100: 6.99

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]

ACMG classification

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 rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	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	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1136T>C	p.Val379Ala	missense_variant	Exon 11 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120206 AN: 152012 Hom.: 47626 Cov.: 33

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

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.: 32 AF XY: 0.807 AC XY: 584403 AN XY: 724066

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.: 33 AF XY: 0.791 AC XY: 58813 AN XY: 74386

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:3 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other: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) -

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). -

RECLASSIFIED - IL4R POLYMORPHISM Benign:1

Jul 01, 2004

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.50	.;T
MetaRNN	Benign	0.0000094	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.42	T
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	T
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

Other links and lift over

dbSNP: rs1051931; hg19: chr6-46672943;