rs3917572

Variant names:

• chr7-95299878-A-G
• rs3917572
• NM_000446.7:c.910-776T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000446.7(PON1):​c.910-776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,110 control chromosomes in the GnomAD database, including 1,251 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 0.11 (1251 hom., cov: 32)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 4 publications found

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]

PON1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.910-776T>C		intron_variant	Intron 8 of 8	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.910-776T>C		intron_variant	Intron 8 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*635-776T>C		intron_variant	Intron 8 of 8	3		ENSP00000407359.1
PON1	ENST00000462594.1	n.200-776T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17032 AN: 151992 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.112 AC: 17065 AN: 152110 Hom.: 1251 Cov.: 32 AF XY: 0.115 AC XY: 8554 AN XY: 74362

African (AFR) AF: 0.196 AC: 8111 AN: 41464

American (AMR) AF: 0.143 AC: 2189 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.134 AC: 690 AN: 5154

South Asian (SAS) AF: 0.0993 AC: 479 AN: 4822

European-Finnish (FIN) AF: 0.113 AC: 1193 AN: 10592

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0570 AC: 3878 AN: 68000

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0827 Hom.: 984

Bravo AF: 0.121

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3917572; hg19: chr7-94929190;