rs3917562

Positions:

• chr7-95303352-ATGCT-A
• chr7-95303352-ATGCT-ATGCTTGCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000222381.8(PON1):​c.781-1023_781-1020del 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 150,578 control chromosomes in the GnomAD database, including 4,053 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4053 hom., cov: 27)
• Consequence: PON1 ENST00000222381.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

PON1 (HGNC:9204): (paraoxonase 1) This gene encodes a member of the paraoxonase family of enzymes and exhibits lactonase and ester hydrolase activity. Following synthesis in the kidney and liver, the enzyme is secreted into the circulation, where it binds to high density lipoprotein (HDL) particles and hydrolyzes thiolactones and xenobiotics, including paraoxon, a metabolite of the insecticide parathion. Polymorphisms in this gene may be associated with coronary artery disease and diabetic retinopathy. The gene is found in a cluster of three related paraoxonase genes on chromosome 7. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.781-1023_781-1020del		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.781-1023_781-1020del		intron_variant		1	NM_000446.7	ENSP00000222381	P1
PON1	ENST00000433729.1	c.*506-1023_*506-1020del		intron_variant, NMD_transcript_variant		3		ENSP00000407359

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32050 AN: 150474 Hom.: 4041 Cov.: 27

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.213 AC: 32099 AN: 150578 Hom.: 4053 Cov.: 27 AF XY: 0.216 AC XY: 15895 AN XY: 73606

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.221

Alfa AF: 0.171 Hom.: 303

Bravo AF: 0.230

Asia WGS AF: 0.371 AC: 1284 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3917562; hg19: chr7-94932664;