7-95298396-T-C

Position:

• chr7-95298396-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.*548A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 165,540 control chromosomes in the GnomAD database, including 1,376 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 0.11 (1195 hom., cov: 32)
  • Exomes 𝑓: 0.13 (181 hom.)
• Consequence: PON1 NM_000446.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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 = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.*548A>G		3_prime_UTR_variant	9/9	ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.*548A>G		3_prime_UTR_variant	9/9	1	NM_000446.7	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16324 AN: 152082 Hom.: 1196 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.128 AC: 1704 AN: 13340 Hom.: 181 Cov.: 0 AF XY: 0.129 AC XY: 897 AN XY: 6980

Gnomad4 AFR exome AF: 0.0619

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0417

Gnomad4 NFE exome AF: 0.0751

Gnomad4 OTH exome AF: 0.0939

GnomAD4 genome AF: 0.107 AC: 16332 AN: 152200 Hom.: 1195 Cov.: 32 AF XY: 0.110 AC XY: 8179 AN XY: 74410

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.134

Alfa AF: 0.107 Hom.: 1785

Bravo AF: 0.115

Asia WGS AF: 0.282 AC: 979 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	0.52
DANN	Benign	0.37

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: rs3917577; hg19: chr7-94927708;