6-46705206-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Benign criteria provided, single submitter B:3 O:1
• Conservation: PhyloP100: 6.99
• Publications: 130 publications found

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

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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	NM_005084.4	MANE Select	c.1136T>C	p.Val379Ala	missense	Exon 11 of 12	NP_005075.3
	PLA2G7	NM_001168357.2		c.1136T>C	p.Val379Ala	missense	Exon 11 of 12	NP_001161829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	ENST00000274793.12	TSL:1 MANE Select	c.1136T>C	p.Val379Ala	missense	Exon 11 of 12	ENSP00000274793.7
	PLA2G7	ENST00000537365.1	TSL:1	c.1136T>C	p.Val379Ala	missense	Exon 11 of 12	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

GnomAD2 exomes AF: 0.805 AC: 201897 AN: 250760 AF XY: 0.805

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

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

GnomAD4 genome AF: 0.791 AC: 120284 AN: 152130 Hom.: 47651 Cov.: 33 AF XY: 0.791 AC XY: 58813 AN XY: 74386

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

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: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)

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 v4.9

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
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
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.20
Sift	Benign	0.32	T
Sift4G	Benign	0.67	T
Polyphen		0.99	D
Vest4		0.29
MPC		0.019
ClinPred		0.043	T
GERP RS		5.9
Varity_R		0.48
gMVP		0.42
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051931; hg19: chr6-46672943; COSMIC: COSV107287160; COSMIC: COSV107287160;