rs3917564

Positions:

• chr7-95302400-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000446.7(PON1):​c.781-67T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,457,726 control chromosomes in the GnomAD database, including 879 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 0.047 (453 hom., cov: 32)
  • Exomes 𝑓: 0.010 (426 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.781-67T>C		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.781-67T>C		intron_variant		1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000462594.1	n.4T>C		non_coding_transcript_exon_variant	1/2	2
PON1	ENST00000433729.1	n.*506-67T>C		intron_variant		3		ENSP00000407359.1

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7099 AN: 152104 Hom.: 447 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0101 AC: 13147 AN: 1305504 Hom.: 426 Cov.: 19 AF XY: 0.00952 AC XY: 6247 AN XY: 656334

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.000120

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.00155

Gnomad4 NFE exome AF: 0.00701

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0468 AC: 7131 AN: 152222 Hom.: 453 Cov.: 32 AF XY: 0.0449 AC XY: 3342 AN XY: 74428

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00723

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0154 Hom.: 103

Bravo AF: 0.0525

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.72

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: rs3917564; hg19: chr7-94931712;