rs3917562

Variant names:

• chr7-95303352-ATGCT-A
• rs3917562
• NM_000446.7:c.781-1023_781-1020delAGCA

Your query was ambiguous. Multiple possible variants found:

• chr7-95303352-ATGCT-A
• chr7-95303352-ATGCT-ATGCTTGCT

Variant summary

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

The NM_000446.7(PON1):​c.781-1023_781-1020delAGCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 150,578 control chromosomes in the GnomAD database, including 4,053 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4053 hom., cov: 27)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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 = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000446.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON1	NM_000446.7	MANE Select	c.781-1023_781-1020delAGCA		intron	N/A	NP_000437.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON1	ENST00000222381.8	TSL:1 MANE Select	c.781-1023_781-1020delAGCA		intron	N/A	ENSP00000222381.3	P27169
	PON1	ENST00000893040.1		c.772-1023_772-1020delAGCA		intron	N/A	ENSP00000563099.1
	PON1	ENST00000893036.1		c.781-1071_781-1068delAGCA		intron	N/A	ENSP00000563095.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32050 AN: 150474 Hom.: 4041 Cov.: 27

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.213 AC: 32099 AN: 150578 Hom.: 4053 Cov.: 27 AF XY: 0.216 AC XY: 15895 AN XY: 73606

African (AFR) AF: 0.295 AC: 11842 AN: 40132

American (AMR) AF: 0.259 AC: 3944 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 802 AN: 3464

East Asian (EAS) AF: 0.548 AC: 2790 AN: 5090

South Asian (SAS) AF: 0.244 AC: 1170 AN: 4804

European-Finnish (FIN) AF: 0.113 AC: 1201 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9787 AN: 67960

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.171 Hom.: 303

Bravo AF: 0.230

Asia WGS AF: 0.371 AC: 1284 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3917562;

hg19: chr7-94932664;