7-95298612-C-T

Position:

• chr7-95298612-C-T

Variant summary

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

The NM_000446.7(PON1):​c.*332G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 385,974 control chromosomes in the GnomAD database, including 96,441 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 0.65 (33094 hom., cov: 31)
  • Exomes 𝑓: 0.73 (63347 hom.)
• Consequence: PON1 NM_000446.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.*332G>A		3_prime_UTR_variant	9/9	ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.*332G>A		3_prime_UTR_variant	9/9	1	NM_000446.7	P1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98112 AN: 151862 Hom.: 33099 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.732 AC: 171203 AN: 233994 Hom.: 63347 Cov.: 2 AF XY: 0.737 AC XY: 93577 AN XY: 126966

Gnomad4 AFR exome AF: 0.437

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.777

Gnomad4 SAS exome AF: 0.773

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.646 AC: 98133 AN: 151980 Hom.: 33094 Cov.: 31 AF XY: 0.647 AC XY: 48075 AN XY: 74274

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.692

Alfa AF: 0.727 Hom.: 68590

Bravo AF: 0.638

Asia WGS AF: 0.728 AC: 2530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.44

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: rs854552; hg19: chr7-94927924;