rs7792044

Positions:

• chr7-95301959-T-C
• chr7-95301959-T-G

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+246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 148,780 control chromosomes in the GnomAD database, including 937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (937 hom., cov: 25)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.418

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=-0.96).
• BP6: Variant 7-95301959-T-C is Benign according to our data. Variant chr7-95301959-T-C is described in ClinVar as [Benign]. Clinvar id is 1233629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON1	NM_000446.7	c.909+246A>G		intron_variant		ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.909+246A>G		intron_variant		1	NM_000446.7	ENSP00000222381	P1
PON1	ENST00000433729.1	c.*634+246A>G		intron_variant, NMD_transcript_variant		3		ENSP00000407359
PON1	ENST00000462594.1	n.199+246A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15152 AN: 148724 Hom.: 934 Cov.: 25

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0901

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15168 AN: 148780 Hom.: 937 Cov.: 25 AF XY: 0.104 AC XY: 7560 AN XY: 72372

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.0782 Hom.: 64

Bravo AF: 0.108

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.7
DANN	Benign	0.18

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: rs7792044; hg19: chr7-94931271;