rs3917486

Positions:

• chr7-95320872-G-A

Variant summary

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

The ENST00000222381.8(PON1):​c.75-2479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 152,314 control chromosomes in the GnomAD database, including 167 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 0.035 (167 hom., cov: 32)
• Consequence: PON1 ENST00000222381.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0351 (5346/152314) while in subpopulation NFE AF= 0.047 (3194/68024). AF 95% confidence interval is 0.0456. There are 167 homozygotes in gnomad4. There are 2697 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 167 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.75-2479C>T		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.75-2479C>T		intron_variant		1	NM_000446.7	ENSP00000222381	P1
PON1	ENST00000433729.1	c.75-2479C>T		intron_variant, NMD_transcript_variant		3		ENSP00000407359

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5348 AN: 152196 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.00786

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0351 AC: 5346 AN: 152314 Hom.: 167 Cov.: 32 AF XY: 0.0362 AC XY: 2697 AN XY: 74472

Gnomad4 AFR AF: 0.00784

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0943

Gnomad4 NFE AF: 0.0470

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0407 Hom.: 19

Bravo AF: 0.0291

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.71

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: rs3917486; hg19: chr7-94950184;