rs2301711

Variant names:

• chr7-95316347-T-C
• rs2301711
• NM_000446.7:c.201+387A>G

Variant summary

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

The NM_000446.7(PON1):​c.201+387A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,128 control chromosomes in the GnomAD database, including 2,530 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 0.14 (2530 hom., cov: 33)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 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.201+387A>G		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.201+387A>G		intron	N/A	ENSP00000222381.3	P27169
	PON1	ENST00000893040.1		c.201+387A>G		intron	N/A	ENSP00000563099.1
	PON1	ENST00000893036.1		c.201+387A>G		intron	N/A	ENSP00000563095.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21598 AN: 152008 Hom.: 2512 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.142 AC: 21651 AN: 152128 Hom.: 2530 Cov.: 33 AF XY: 0.142 AC XY: 10527 AN XY: 74374

African (AFR) AF: 0.314 AC: 13012 AN: 41440

American (AMR) AF: 0.149 AC: 2282 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.138 AC: 712 AN: 5176

South Asian (SAS) AF: 0.125 AC: 604 AN: 4822

European-Finnish (FIN) AF: 0.0710 AC: 752 AN: 10590

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3735 AN: 68028

Other (OTH) AF: 0.122 AC: 259 AN: 2116

Alfa AF: 0.0873 Hom.: 1319

Bravo AF: 0.158

Asia WGS AF: 0.138 AC: 479 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.58
PhyloP100		-1.8
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: rs2301711; hg19: chr7-94945659;