rs17886586

Positions:

• chr7-95396381-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The 7-95396381-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,608,114 control chromosomes in the GnomAD database, including 302 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 0.011 (29 hom., cov: 31)
  • Exomes 𝑓: 0.015 (273 hom.)
• Consequence: PON3 NM_000940.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

Genes affected

PON3 (HGNC:9206): (paraoxonase 3) This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with high-density lipoprotein (HDL). The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of low-density lipoprotein (LDL), a function that is believed to slow the initiation and progression of atherosclerosis. Alternatively spliced variants which encode different protein isoforms have been described; however, only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0113 (1724/152114) while in subpopulation SAS AF= 0.0475 (229/4816). AF 95% confidence interval is 0.0425. There are 29 homozygotes in gnomad4. There are 861 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3			upstream_gene_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10			upstream_gene_variant		1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1718 AN: 152000 Hom.: 28 Cov.: 31

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0196 AC: 4820 AN: 245410 Hom.: 78 AF XY: 0.0201 AC XY: 2678 AN XY: 133336

Gnomad AFR exome AF: 0.00273

Gnomad AMR exome AF: 0.0430

Gnomad ASJ exome AF: 0.00673

Gnomad EAS exome AF: 0.0181

Gnomad SAS exome AF: 0.0462

Gnomad FIN exome AF: 0.00540

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.0141

GnomAD4 exome AF: 0.0151 AC: 21934 AN: 1456000 Hom.: 273 Cov.: 31 AF XY: 0.0157 AC XY: 11395 AN XY: 724626

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.0412

Gnomad4 ASJ exome AF: 0.00614

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.00592

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0113 AC: 1724 AN: 152114 Hom.: 29 Cov.: 31 AF XY: 0.0116 AC XY: 861 AN XY: 74350

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0163

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0139 Hom.: 10

Bravo AF: 0.0126

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17886586; hg19: chr7-95025693;