rs854562

Positions:

• chr7-95318657-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000446.7(PON1):​c.75-264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 396,058 control chromosomes in the GnomAD database, including 15,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5234 hom., cov: 32)
  • Exomes 𝑓: 0.28 (10655 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.209

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-95318657-C-T is Benign according to our data. Variant chr7-95318657-C-T is described in ClinVar as [Benign]. Clinvar id is 1284201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.75-264G>A		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.75-264G>A		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.75-264G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35890 AN: 151926 Hom.: 5234 Cov.: 32

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.281 AC: 68649 AN: 244014 Hom.: 10655 AF XY: 0.277 AC XY: 36219 AN XY: 130798

Gnomad4 AFR exome AF: 0.0801

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.0533

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.236 AC: 35889 AN: 152044 Hom.: 5234 Cov.: 32 AF XY: 0.235 AC XY: 17433 AN XY: 74304

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.269

Alfa AF: 0.310 Hom.: 9704

Bravo AF: 0.224

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.60

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: rs854562; hg19: chr7-94947969;