rs2301711

chr7-95316347-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.201+387A>G		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.201+387A>G		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.201+387A>G		intron_variant, NMD_transcript_variant		3
PON1	ENST00000470502.1	n.321+387A>G		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0710

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0759 Hom.: 735

Bravo AF: 0.158

Asia WGS AF: 0.138 AC: 479 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.15
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs2301711; hg19: chr7-94945659;