6-46716485-C-T

Variant names:

• chr6-46716485-C-T
• rs1805017
• NM_005084.4:c.275G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005084.4(PLA2G7):​c.275G>A​(p.Arg92His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,612,368 control chromosomes in the GnomAD database, including 65,276 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). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.28 (6251 hom., cov: 32)
  • Exomes 𝑓: 0.28 (59025 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: -2.83

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.055892E-5).
• BP6: Variant 6-46716485-C-T is Benign according to our data. Variant chr6-46716485-C-T is described in ClinVar as [Benign]. Clinvar id is 56163.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-46716485-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.275G>A	p.Arg92His	missense_variant	Exon 4 of 12	ENST00000274793.12	NP_005075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.275G>A	p.Arg92His	missense_variant	Exon 4 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.275G>A	p.Arg92His	missense_variant	Exon 4 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42968 AN: 151864 Hom.: 6253 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.295

GnomAD3 exomes AF: 0.308 AC: 77285 AN: 251194 Hom.: 13047 AF XY: 0.313 AC XY: 42548 AN XY: 135752

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.507

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.276 AC: 402482 AN: 1460386 Hom.: 59025 Cov.: 33 AF XY: 0.282 AC XY: 205112 AN XY: 726582

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.283 AC: 43002 AN: 151982 Hom.: 6251 Cov.: 32 AF XY: 0.287 AC XY: 21331 AN XY: 74266

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.299

Alfa AF: 0.262 Hom.: 12259

Bravo AF: 0.279

TwinsUK AF: 0.255 AC: 947

ALSPAC AF: 0.257 AC: 989

ESP6500AA AF: 0.276 AC: 1216

ESP6500EA AF: 0.262 AC: 2250

ExAC AF: 0.303 AC: 36807

Asia WGS AF: 0.375 AC: 1303 AN: 3478

EpiCase AF: 0.268

EpiControl AF: 0.262

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

PLA2G7-related disorder Benign:1

Oct 22, 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). -

not provided Other:1

-

Lab. of Molecular Biology of Arterial Hypertension University of Padova

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.041
DANN	Benign	0.81
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.16	.;T
MetaRNN	Benign	0.000051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.51	N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.61	N;N
REVEL	Benign	0.057
Sift	Benign	0.59	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.0	B;B
Vest4		0.062
MPC		0.0045
ClinPred		0.017	T
GERP RS		-10
Varity_R		0.30
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1805017; hg19: chr6-46684222; COSMIC: COSV51259326;