7-95299242-AAC-A

Variant summary

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

The NM_000446.7(PON1):c.910-142_910-141del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 901,492 control chromosomes in the GnomAD database, including 3,142 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (811 hom., cov: 31)
  • Exomes 𝑓: 0.065 (2331 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329

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 7-95299242-AAC-A is Benign according to our data. Variant chr7-95299242-AAC-A is described in ClinVar as [Benign]. Clinvar id is 1283625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.910-142_910-141del		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.910-142_910-141del		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*635-142_*635-141del		intron_variant, NMD_transcript_variant		3
PON1	ENST00000462594.1	n.200-142_200-141del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14087 AN: 152090 Hom.: 806 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0824

GnomAD4 exome AF: 0.0650 AC: 48698 AN: 749286 Hom.: 2331 AF XY: 0.0635 AC XY: 25111 AN XY: 395454

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.0673

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0611

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0720

GnomAD4 genome AF: 0.0927 AC: 14113 AN: 152206 Hom.: 811 Cov.: 31 AF XY: 0.0953 AC XY: 7095 AN XY: 74422

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0815

Alfa AF: 0.0747 Hom.: 66

Bravo AF: 0.0990

Asia WGS AF: 0.0940 AC: 327 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs3917574; hg19: chr7-94928554;