NM_005084.4:c.-34-5845A>C

Variant names:

• chr6-46728770-T-G
• rs12528807
• NM_005084.4:c.-34-5845A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005084.4(PLA2G7):​c.-34-5845A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 152,294 control chromosomes in the GnomAD database, including 370 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.058 (370 hom., cov: 33)
• Consequence: PLA2G7 NM_005084.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.-34-5845A>C		intron_variant	Intron 1 of 11	ENST00000274793.12	NP_005075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.-34-5845A>C		intron_variant	Intron 1 of 11	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.-34-5845A>C		intron_variant	Intron 1 of 11	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8849 AN: 152176 Hom.: 371 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0737

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0581 AC: 8841 AN: 152294 Hom.: 370 Cov.: 33 AF XY: 0.0572 AC XY: 4258 AN XY: 74466

African (AFR) AF: 0.0131 AC: 544 AN: 41572

American (AMR) AF: 0.0554 AC: 847 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0949 AC: 458 AN: 4828

European-Finnish (FIN) AF: 0.0636 AC: 674 AN: 10598

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5568 AN: 68026

Other (OTH) AF: 0.0724 AC: 153 AN: 2112

Alfa AF: 0.0779 Hom.: 859

Bravo AF: 0.0531

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.85
PhyloP100		1.3
Mutation Taster		=100/0	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: rs12528807; hg19: chr6-46696507;