7-95301959-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.418

Publications

3 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
PON1NM_000446.7 linkc.909+246A>G intron_variant Intron 8 of 8 ENST00000222381.8 NP_000437.3 P27169

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PON1ENST00000222381.8 linkc.909+246A>G intron_variant Intron 8 of 8 1 NM_000446.7 ENSP00000222381.3 P27169
PON1ENST00000433729.1 linkn.*634+246A>G intron_variant Intron 8 of 8 3 ENSP00000407359.1 F8WF42
PON1ENST00000462594.1 linkn.199+246A>G intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15152
AN:
148724
Hom.:
934
Cov.:
25
show subpopulations
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
show subpopulations
African (AFR)
AF:
0.153
AC:
6202
AN:
40438
American (AMR)
AF:
0.136
AC:
2039
AN:
14996
Ashkenazi Jewish (ASJ)
AF:
0.0692
AC:
239
AN:
3452
East Asian (EAS)
AF:
0.118
AC:
592
AN:
5036
South Asian (SAS)
AF:
0.0726
AC:
340
AN:
4680
European-Finnish (FIN)
AF:
0.124
AC:
1186
AN:
9590
Middle Eastern (MID)
AF:
0.0870
AC:
24
AN:
276
European-Non Finnish (NFE)
AF:
0.0642
AC:
4325
AN:
67356
Other (OTH)
AF:
0.0894
AC:
183
AN:
2046
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
617
1233
1850
2466
3083
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
166
332
498
664
830
<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:
0.0801
Hom.:
71
Bravo
AF:
0.108

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
BayesDel_noAF
Benign
-0.96
CADD
Benign
3.7
DANN
Benign
0.18
PhyloP100
0.42
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7792044; hg19: chr7-94931271; API