rs3917493
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000446.7(PON1):c.75-323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 280,878 control chromosomes in the GnomAD database, including 1,051 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 0.084 ( 674 hom., cov: 32)
Exomes 𝑓: 0.065 ( 377 hom. )
Consequence
PON1
NM_000446.7 intron
NM_000446.7 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.216
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PON1 | NM_000446.7 | c.75-323A>G | intron_variant | ENST00000222381.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PON1 | ENST00000222381.8 | c.75-323A>G | intron_variant | 1 | NM_000446.7 | P1 | |||
PON1 | ENST00000433729.1 | c.75-323A>G | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0839 AC: 12766AN: 152098Hom.: 672 Cov.: 32
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GnomAD4 exome AF: 0.0652 AC: 8392AN: 128662Hom.: 377 AF XY: 0.0653 AC XY: 4467AN XY: 68454
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GnomAD4 genome ? AF: 0.0840 AC: 12784AN: 152216Hom.: 674 Cov.: 32 AF XY: 0.0844 AC XY: 6282AN XY: 74432
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at