6-46704644-C-A

Variant names:

• chr6-46704644-C-A
• rs145290218
• NM_005084.4:c.1242G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005084.4(PLA2G7):​c.1242G>T​(p.Glu414Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,577,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00060 (0 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.05
• Publications: 7 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01131922).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	NM_005084.4	MANE Select	c.1242G>T	p.Glu414Asp	missense	Exon 12 of 12	NP_005075.3
	PLA2G7	NM_001168357.2		c.1242G>T	p.Glu414Asp	missense	Exon 12 of 12	NP_001161829.1	Q13093

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	ENST00000274793.12	TSL:1 MANE Select	c.1242G>T	p.Glu414Asp	missense	Exon 12 of 12	ENSP00000274793.7	Q13093
	PLA2G7	ENST00000537365.1	TSL:1	c.1242G>T	p.Glu414Asp	missense	Exon 12 of 12	ENSP00000445666.1	Q13093
	PLA2G7	ENST00000878321.1		c.1242G>T	p.Glu414Asp	missense	Exon 12 of 12	ENSP00000548380.1

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 92 AN: 152074 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000526 AC: 132 AN: 250988 AF XY: 0.000494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000599 AC: 854 AN: 1425692 Hom.: 0 Cov.: 27 AF XY: 0.000568 AC XY: 404 AN XY: 711720

African (AFR) AF: 0.0000912 AC: 3 AN: 32878

American (AMR) AF: 0.00135 AC: 60 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.00 AC: 0 AN: 85598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5716

European-Non Finnish (NFE) AF: 0.000698 AC: 753 AN: 1078960

Other (OTH) AF: 0.000625 AC: 37 AN: 59190

GnomAD4 genome AF: 0.000605 AC: 92 AN: 152192 Hom.: 0 Cov.: 31 AF XY: 0.000618 AC XY: 46 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41514

American (AMR) AF: 0.00203 AC: 31 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000670 Hom.: 0

Bravo AF: 0.000597

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000437 AC: 53

EpiCase AF: 0.00104

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.5
DANN	Benign	0.55
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.39	N
PhyloP100		-1.1
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.090
Sift	Benign	0.47	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.54		Loss of disorder (P = 0.277)
MVP		0.24
MPC		0.0051
ClinPred		0.0091	T
GERP RS		-5.9
Varity_R		0.16
gMVP		0.33
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs145290218; hg19: chr6-46672381;