rs3735590

chr7-95298183-G-A

Variant summary

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

The NM_000446.7(PON1):c.*761C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,558 control chromosomes in the GnomAD database, including 2,291 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 0.14 (2291 hom., cov: 32)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: PON1 NM_000446.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.*761C>T		3_prime_UTR_variant	9/9	ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.*761C>T		3_prime_UTR_variant	9/9	1	NM_000446.7	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21295 AN: 152000 Hom.: 2274 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0432 AC: 19 AN: 440 Hom.: 0 Cov.: 0 AF XY: 0.0424 AC XY: 10 AN XY: 236

Gnomad4 AMR exome AF: 0.0769

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0335

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.140 AC: 21359 AN: 152118 Hom.: 2291 Cov.: 32 AF XY: 0.142 AC XY: 10528 AN XY: 74374

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0619

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0803 Hom.: 989

Bravo AF: 0.152

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.021
Dann	Benign	0.58

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: rs3735590; hg19: chr7-94927495;