rs3917515

Variant names:

• chr7-95312771-G-A
• rs3917515
• NM_000446.7:c.371-1194C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-95312771-G-A
• chr7-95312771-G-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.371-1194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 151,642 control chromosomes in the GnomAD database, including 747 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 0.087 (747 hom., cov: 32)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.371-1194C>T		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.371-1194C>T		intron_variant	Intron 4 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*96-1194C>T		intron_variant	Intron 4 of 8	3		ENSP00000407359.1
PON1	ENST00000470502.1	n.491-1194C>T		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13177 AN: 151524 Hom.: 744 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0786

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

GnomAD4 genome AF: 0.0870 AC: 13195 AN: 151642 Hom.: 747 Cov.: 32 AF XY: 0.0873 AC XY: 6472 AN XY: 74136

African (AFR) AF: 0.139 AC: 5701 AN: 41082

American (AMR) AF: 0.122 AC: 1853 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3472

East Asian (EAS) AF: 0.117 AC: 604 AN: 5142

South Asian (SAS) AF: 0.0708 AC: 340 AN: 4804

European-Finnish (FIN) AF: 0.0686 AC: 727 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0520 AC: 3534 AN: 67980

Other (OTH) AF: 0.0778 AC: 164 AN: 2108

Alfa AF: 0.0254 Hom.: 17

Bravo AF: 0.0968

Asia WGS AF: 0.0940 AC: 328 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.42
PhyloP100		0.0
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: rs3917515; hg19: chr7-94942083;