6-46731555-C-T

Position:

• chr6-46731555-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005084.4(PLA2G7):​c.-35+3625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,900 control chromosomes in the GnomAD database, including 3,834 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 0.21 (3834 hom., cov: 32)
• Consequence: PLA2G7 NM_005084.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G7	NM_005084.4	c.-35+3625G>A		intron_variant		ENST00000274793.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G7	ENST00000274793.12	c.-35+3625G>A		intron_variant		1	NM_005084.4	P1
PLA2G7	ENST00000537365.1	c.-35+3995G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32254 AN: 151784 Hom.: 3825 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.213 AC: 32290 AN: 151900 Hom.: 3834 Cov.: 32 AF XY: 0.220 AC XY: 16295 AN XY: 74214

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.233

Alfa AF: 0.210 Hom.: 471

Bravo AF: 0.205

Asia WGS AF: 0.326 AC: 1131 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs9381475; hg19: chr6-46699292;