dbSNP rs705379: PON1:c.-108C>T (chr7-95324583-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000446.7(PON1):c.-108C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,123,462 control chromosomes in the GnomAD database, including 117,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12486 hom., cov: 32)

Exomes 𝑓: 0.46 ( 104557 hom. )

Consequence

PON1
NM_000446.7 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.13

Variant links:

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]

PON1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-95324583-G-A is Benign according to our data. Variant chr7-95324583-G-A is described in ClinVar as [Benign]. Clinvar id is 13737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7 link	c.-108C>T		upstream_gene_variant		ENST00000222381.8	NP_000437.3	P27169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8 link	c.-108C>T		upstream_gene_variant		1	NM_000446.7	ENSP00000222381.3		P27169
PON1	ENST00000433729.1 link	n.-108C>T		upstream_gene_variant		3		ENSP00000407359.1		F8WF42

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56913

AN:

151920

Hom.:

12490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.435

GnomAD4 exome

AF:

0.458

AC:

444754

AN:

971426

Hom.:

104557

Cov.:

AF XY:

0.458

AC XY:

227112

AN XY:

496168

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.401

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.476

Gnomad4 OTH exome

AF:

0.455

GnomAD4 genome

AF:

0.374

AC:

56917

AN:

152036

Hom.:

12486

Cov.:

AF XY:

0.373

AC XY:

27745

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.480

Gnomad4 OTH

AF:

0.435

Alfa

AF:

0.408

Hom.:

1946

Bravo

AF:

0.376

Asia WGS

AF:

0.387

AC:

1348

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26154629, 11335891, 10669651) -

Enzyme activity finding

Other:1

Aug 18, 2014

OMIM

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.9

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over