Genetic Variant PON1:c.910-142_910-141delGT (chr7-95299242-AAC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000446.7(PON1):c.910-142_910-141delGT 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.329

Publications

1 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 -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 rank	MANE	Protein	UniProt
PON1	NM_000446.7 link	c.910-142_910-141delGT		intron_variant	Intron 8 of 8	ENST00000222381.8	NP_000437.3	P27169

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PON1	ENST00000222381.8 link	c.910-142_910-141delGT	intron_variant	Intron 8 of 8	1	NM_000446.7	ENSP00000222381.3	P27169
PON1	ENST00000433729.1 link	n.635-142_635-141delGT	intron_variant	Intron 8 of 8	3		ENSP00000407359.1	F8WF42
PON1	ENST00000462594.1 link	n.200-142_200-141delGT	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0926

AC:

14087

AN:

152090

Hom.:

806

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.133

AC:

2556

AN:

19210

American (AMR)

AF:

0.180

AC:

6647

AN:

36914

Ashkenazi Jewish (ASJ)

AF:

0.0673

AC:

1371

AN:

20370

East Asian (EAS)

AF:

0.112

AC:

3896

AN:

34674

South Asian (SAS)

AF:

0.0611

AC:

4035

AN:

65988

European-Finnish (FIN)

AF:

0.103

AC:

3771

AN:

36484

Middle Eastern (MID)

AF:

0.0654

AC:

267

AN:

4082

European-Non Finnish (NFE)

AF:

0.0475

AC:

23497

AN:

494664

Other (OTH)

AF:

0.0720

AC:

2658

AN:

36900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2354

4707

7061

9414

11768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0927

AC:

14113

AN:

152206

Hom.:

811

Cov.:

AF XY:

0.0953

AC XY:

7095

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.141

AC:

5874

AN:

41516

American (AMR)

AF:

0.126

AC:

1933

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

609

AN:

5174

South Asian (SAS)

AF:

0.0693

AC:

334

AN:

4820

European-Finnish (FIN)

AF:

0.110

AC:

1166

AN:

10602

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0549

AC:

3734

AN:

68022

Other (OTH)

AF:

0.0815

AC:

172

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

617

1235

1852

2470

3087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0747

Hom.:

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-95299242-AAC-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over