7-95365242-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000940.3(PON3):​c.495-1179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,116 control chromosomes in the GnomAD database, including 15,819 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 0.44 ( 15807 hom., cov: 32)
Exomes 𝑓: 0.40 ( 12 hom. )

Consequence

PON3
NM_000940.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49
Variant links:
Genes affected
PON3 (HGNC:9206): (paraoxonase 3) This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with high-density lipoprotein (HDL). The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of low-density lipoprotein (LDL), a function that is believed to slow the initiation and progression of atherosclerosis. Alternatively spliced variants which encode different protein isoforms have been described; however, only one has been fully characterized. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PON3NM_000940.3 linkuse as main transcriptc.495-1179A>G intron_variant ENST00000265627.10 NP_000931.1 Q15166

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PON3ENST00000265627.10 linkuse as main transcriptc.495-1179A>G intron_variant 1 NM_000940.3 ENSP00000265627.5 Q15166

Frequencies

GnomAD3 genomes
AF:
0.441
AC:
66961
AN:
151908
Hom.:
15800
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.293
Gnomad AMI
AF:
0.613
Gnomad AMR
AF:
0.541
Gnomad ASJ
AF:
0.404
Gnomad EAS
AF:
0.739
Gnomad SAS
AF:
0.618
Gnomad FIN
AF:
0.591
Gnomad MID
AF:
0.395
Gnomad NFE
AF:
0.450
Gnomad OTH
AF:
0.433
GnomAD4 exome
AF:
0.400
AC:
36
AN:
90
Hom.:
12
Cov.:
0
AF XY:
0.482
AC XY:
27
AN XY:
56
show subpopulations
Gnomad4 AFR exome
AF:
0.333
Gnomad4 AMR exome
AF:
0.500
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
0.750
Gnomad4 NFE exome
AF:
0.368
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.441
AC:
66989
AN:
152026
Hom.:
15807
Cov.:
32
AF XY:
0.455
AC XY:
33824
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.292
Gnomad4 AMR
AF:
0.541
Gnomad4 ASJ
AF:
0.404
Gnomad4 EAS
AF:
0.739
Gnomad4 SAS
AF:
0.619
Gnomad4 FIN
AF:
0.591
Gnomad4 NFE
AF:
0.450
Gnomad4 OTH
AF:
0.439
Alfa
AF:
0.428
Hom.:
2116
Bravo
AF:
0.430
Asia WGS
AF:
0.650
AC:
2257
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
3.0
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs9640632; hg19: chr7-94994554; COSMIC: COSV55698906; COSMIC: COSV55698906; API