rs59551306

Positions:

• chr7-95302113-AAAAAAAAAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000446.7(PON1):​c.909+83_909+91del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 843,618 control chromosomes in the GnomAD database, including 915 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (384 hom., cov: 16)
  • Exomes 𝑓: 0.060 (531 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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 -10 ACMG points.

• BP6: Variant 7-95302113-AAAAAAAAAC-A is Benign according to our data. Variant chr7-95302113-AAAAAAAAAC-A is described in ClinVar as [Benign]. Clinvar id is 1267129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.909+83_909+91del		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.909+83_909+91del		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*634+83_*634+91del		intron_variant, NMD_transcript_variant		3
PON1	ENST00000462594.1	n.199+83_199+91del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10092 AN: 143552 Hom.: 381 Cov.: 16

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0365

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0774

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0629

GnomAD4 exome AF: 0.0603 AC: 42232 AN: 699988 Hom.: 531 AF XY: 0.0591 AC XY: 21151 AN XY: 358094

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.0637

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.0461

Gnomad4 FIN exome AF: 0.0863

Gnomad4 NFE exome AF: 0.0532

Gnomad4 OTH exome AF: 0.0665

GnomAD4 genome AF: 0.0703 AC: 10098 AN: 143630 Hom.: 384 Cov.: 16 AF XY: 0.0694 AC XY: 4838 AN XY: 69674

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0933

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.0554

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.0622

Alfa AF: 0.0556 Hom.: 5

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59551306; hg19: chr7-94931425; COSMIC: COSV55933038;