Genetic Variant NM_000446.7:c.909+83_909+91delGTTTTTTTT (chr7-95302113-AAAAAAAAAC-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.909+83_909+91delGTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 843,618 control chromosomes in the GnomAD database, including 915 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.070 ( 384 hom., cov: 16)

Exomes 𝑓: 0.060 ( 531 hom. )

Consequence

PON1
NM_000446.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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 7-95302113-AAAAAAAAAC-A is Benign according to our data. Variant chr7-95302113-AAAAAAAAAC-A is described in ClinVar as [Benign]. Clinvar id is 1267129.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7 link	c.909+83_909+91delGTTTTTTTT		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.909+83_909+91delGTTTTTTTT	intron_variant	Intron 8 of 8	1	NM_000446.7	ENSP00000222381.3	P27169
PON1	ENST00000433729.1 link	n.634+83_634+91delGTTTTTTTT	intron_variant	Intron 8 of 8	3		ENSP00000407359.1	F8WF42
PON1	ENST00000462594.1 link	n.199+83_199+91delGTTTTTTTT	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0703

AC:

10092

AN:

143552

Hom.:

381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0365

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0894

Gnomad SAS

AF:

0.0565

Gnomad FIN

AF:

0.0533

Gnomad MID

AF:

0.0774

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0629

GnomAD4 exome

AF:

0.0603

AC:

42232

AN:

699988

Hom.:

531

AF XY:

0.0591

AC XY:

21151

AN XY:

358094

show subpopulations

African (AFR)

AF:

0.130

AC:

1877

AN:

14440

American (AMR)

AF:

0.158

AC:

2820

AN:

17866

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

831

AN:

13048

East Asian (EAS)

AF:

0.133

AC:

1943

AN:

14660

South Asian (SAS)

AF:

0.0461

AC:

2366

AN:

51284

European-Finnish (FIN)

AF:

0.0863

AC:

1811

AN:

20974

Middle Eastern (MID)

AF:

0.0521

AC:

137

AN:

2632

European-Non Finnish (NFE)

AF:

0.0532

AC:

28508

AN:

535922

Other (OTH)

AF:

0.0665

AC:

1939

AN:

29162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

1268

2536

3805

5073

6341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0703

AC:

10098

AN:

143630

Hom.:

384

Cov.:

AF XY:

0.0694

AC XY:

4838

AN XY:

69674

show subpopulations

African (AFR)

AF:

0.103

AC:

3945

AN:

38198

American (AMR)

AF:

0.0933

AC:

1316

AN:

14108

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

194

AN:

3386

East Asian (EAS)

AF:

0.0891

AC:

417

AN:

4682

South Asian (SAS)

AF:

0.0554

AC:

257

AN:

4636

European-Finnish (FIN)

AF:

0.0533

AC:

477

AN:

8950

Middle Eastern (MID)

AF:

0.0799

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0498

AC:

3312

AN:

66486

Other (OTH)

AF:

0.0622

AC:

124

AN:

1992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

293

586

880

1173

1466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0556

Hom.:

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

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_000446.7:c.909+83_909+91delGTTTTTTTT

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