7-95302075-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.909+130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 923,172 control chromosomes in the GnomAD database, including 3,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (667 hom., cov: 21)
  • Exomes 𝑓: 0.056 (2523 hom.)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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=-1.02).
• BP6: Variant 7-95302075-C-T is Benign according to our data. Variant chr7-95302075-C-T is described in ClinVar as [Benign]. Clinvar id is 1228238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7	c.909+130G>A		intron_variant		ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON1	ENST00000222381.8	c.909+130G>A		intron_variant		1	NM_000446.7	P1
PON1	ENST00000433729.1	c.*634+130G>A		intron_variant, NMD_transcript_variant		3
PON1	ENST00000462594.1	n.199+130G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 11687 AN: 116622 Hom.: 666 Cov.: 21

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0676

Gnomad EAS AF: 0.0417

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0832

GnomAD4 exome AF: 0.0564 AC: 45474 AN: 806522 Hom.: 2523 AF XY: 0.0577 AC XY: 23838 AN XY: 413356

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0686

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.0281

Gnomad4 SAS exome AF: 0.0813

Gnomad4 FIN exome AF: 0.0696

Gnomad4 NFE exome AF: 0.0513

Gnomad4 OTH exome AF: 0.0589

GnomAD4 genome AF: 0.100 AC: 11702 AN: 116650 Hom.: 667 Cov.: 21 AF XY: 0.106 AC XY: 5691 AN XY: 53656

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0676

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0188 Hom.: 12

Bravo AF: 0.0867

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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.7
Dann	Benign	0.80

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: rs7809060; hg19: chr7-94931387;