dbSNP rs3735590: PON1:c.*761C>T (chr7-95298183-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000446.7(PON1):c.*761C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,558 control chromosomes in the GnomAD database, including 2,291 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2291 hom., cov: 32)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

PON1
NM_000446.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.29

Publications

27 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PON1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7 link	c.*761C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000222381.8	NP_000437.3	P27169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8 link	c.*761C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000446.7	ENSP00000222381.3		P27169

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21295

AN:

152000

Hom.:

2274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.116

GnomAD4 exome

AF:

0.0432

AC:

AN:

440

Hom.:

Cov.:

AF XY:

0.0424

AC XY:

AN XY:

236

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0769

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0335

AC:

AN:

358

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.140

AC:

21359

AN:

152118

Hom.:

2291

Cov.:

AF XY:

0.142

AC XY:

10528

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.294

AC:

12207

AN:

41478

American (AMR)

AF:

0.148

AC:

2267

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

610

AN:

5168

South Asian (SAS)

AF:

0.0701

AC:

337

AN:

4810

European-Finnish (FIN)

AF:

0.112

AC:

1182

AN:

10574

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0619

AC:

4211

AN:

68018

Other (OTH)

AF:

0.115

AC:

243

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

851

1701

2552

3402

4253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0882

Hom.:

1563

Bravo

AF:

0.152

Asia WGS

AF:

0.101

AC:

353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.021

(source)

DANN

Benign

0.58

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over