7-95298396-T-C

Variant summary

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

The NM_000446.7(PON1):​c.*548A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 165,540 control chromosomes in the GnomAD database, including 1,376 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 0.11 ( 1195 hom., cov: 32)
Exomes 𝑓: 0.13 ( 181 hom. )

Consequence

PON1
NM_000446.7 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492
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]

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=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PON1NM_000446.7 linkuse as main transcriptc.*548A>G 3_prime_UTR_variant 9/9 ENST00000222381.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PON1ENST00000222381.8 linkuse as main transcriptc.*548A>G 3_prime_UTR_variant 9/91 NM_000446.7 P1

Frequencies

GnomAD3 genomes
AF:
0.107
AC:
16324
AN:
152082
Hom.:
1196
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0855
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.136
Gnomad ASJ
AF:
0.185
Gnomad EAS
AF:
0.415
Gnomad SAS
AF:
0.157
Gnomad FIN
AF:
0.0466
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.0933
Gnomad OTH
AF:
0.133
GnomAD4 exome
AF:
0.128
AC:
1704
AN:
13340
Hom.:
181
Cov.:
0
AF XY:
0.129
AC XY:
897
AN XY:
6980
show subpopulations
Gnomad4 AFR exome
AF:
0.0619
Gnomad4 AMR exome
AF:
0.132
Gnomad4 ASJ exome
AF:
0.116
Gnomad4 EAS exome
AF:
0.415
Gnomad4 SAS exome
AF:
0.140
Gnomad4 FIN exome
AF:
0.0417
Gnomad4 NFE exome
AF:
0.0751
Gnomad4 OTH exome
AF:
0.0939
GnomAD4 genome
AF:
0.107
AC:
16332
AN:
152200
Hom.:
1195
Cov.:
32
AF XY:
0.110
AC XY:
8179
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.0855
Gnomad4 AMR
AF:
0.136
Gnomad4 ASJ
AF:
0.185
Gnomad4 EAS
AF:
0.415
Gnomad4 SAS
AF:
0.158
Gnomad4 FIN
AF:
0.0466
Gnomad4 NFE
AF:
0.0933
Gnomad4 OTH
AF:
0.134
Alfa
AF:
0.107
Hom.:
1785
Bravo
AF:
0.115
Asia WGS
AF:
0.282
AC:
979
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.52
DANN
Benign
0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3917577; hg19: chr7-94927708; API