6-46735776-A-G

Variant names:

• chr6-46735776-A-G
• rs1421378
• ENST00000537365.1:c.-261T>C

Variant summary

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

The NM_001168357.2(PLA2G7):​c.-261T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,160 control chromosomes in the GnomAD database, including 22,448 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 0.51 (22445 hom., cov: 33)
  • Exomes 𝑓: 0.26 (3 hom.)
• Consequence: PLA2G7 NM_001168357.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 29 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168357.2. 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_001168357.2		c.-261T>C		upstream_gene	N/A	NP_001161829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	ENST00000537365.1	TSL:1	c.-261T>C		upstream_gene	N/A	ENSP00000445666.1
	PLA2G7	ENST00000878321.1		c.-193T>C		upstream_gene	N/A	ENSP00000548380.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77804 AN: 152000 Hom.: 22398 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.262 AC: 11 AN: 42 Hom.: 3 AF XY: 0.281 AC XY: 9 AN XY: 32

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 8 AN: 32

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.512 AC: 77909 AN: 152118 Hom.: 22445 Cov.: 33 AF XY: 0.511 AC XY: 37996 AN XY: 74368

African (AFR) AF: 0.777 AC: 32228 AN: 41496

American (AMR) AF: 0.513 AC: 7839 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5160

South Asian (SAS) AF: 0.663 AC: 3201 AN: 4828

European-Finnish (FIN) AF: 0.352 AC: 3722 AN: 10582

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26153 AN: 67986

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.433 Hom.: 44194

Bravo AF: 0.528

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.39
PhyloP100		-1.5
PromoterAI		-0.0048	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1421378; hg19: chr6-46703513;