rs3917506

Variant names:

• chr7-95314871-GA-G
• rs3917506
• NM_000446.7:c.370+450delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000446.7(PON1):​c.370+450delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,018 control chromosomes in the GnomAD database, including 5,243 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5243 hom., cov: 23)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.370+450delT		intron_variant	Intron 4 of 8	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.370+450delT		intron_variant	Intron 4 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*95+450delT		intron_variant	Intron 4 of 8	3		ENSP00000407359.1
PON1	ENST00000470502.1	n.490+450delT		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38553 AN: 151898 Hom.: 5237 Cov.: 23

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.254 AC: 38580 AN: 152018 Hom.: 5243 Cov.: 23 AF XY: 0.257 AC XY: 19078 AN XY: 74326

African (AFR) AF: 0.162 AC: 6727 AN: 41458

American (AMR) AF: 0.284 AC: 4347 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2607 AN: 5144

South Asian (SAS) AF: 0.274 AC: 1321 AN: 4820

European-Finnish (FIN) AF: 0.261 AC: 2763 AN: 10566

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18897 AN: 67960

Other (OTH) AF: 0.275 AC: 580 AN: 2106

Alfa AF: 0.254 Hom.: 640

Bravo AF: 0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.10
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: rs3917506; hg19: chr7-94944183;