chr6-46728605-A-T

Position:

• chr6-46728605-A-T

Variant summary

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

The NM_005084.4(PLA2G7):​c.-34-5680T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,158 control chromosomes in the GnomAD database, including 3,745 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 (3745 hom., cov: 32)
• Consequence: PLA2G7 NM_005084.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.-34-5680T>A		intron_variant		ENST00000274793.12	NP_005075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.-34-5680T>A		intron_variant		1	NM_005084.4	ENSP00000274793	P1
PLA2G7	ENST00000537365.1	c.-34-5680T>A		intron_variant		1		ENSP00000445666	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31639 AN: 152040 Hom.: 3737 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.208 AC: 31668 AN: 152158 Hom.: 3745 Cov.: 32 AF XY: 0.215 AC XY: 15970 AN XY: 74380

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.229

Alfa AF: 0.121 Hom.: 231

Bravo AF: 0.200

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.74

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: rs10948300; hg19: chr6-46696342; COSMIC: COSV51264188;