chr7-95308100-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_000446.7(PON1):c.609G>A(p.Ser203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
PON1
NM_000446.7 synonymous
NM_000446.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.685
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 7-95308100-C-T is Benign according to our data. Variant chr7-95308100-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058100.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.685 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PON1 | NM_000446.7 | c.609G>A | p.Ser203= | synonymous_variant | 6/9 | ENST00000222381.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PON1 | ENST00000222381.8 | c.609G>A | p.Ser203= | synonymous_variant | 6/9 | 1 | NM_000446.7 | P1 | |
PON1 | ENST00000433729.1 | c.*334G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/9 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251366Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135850
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GnomAD4 exome AF: 0.000155 AC: 226AN: 1461806Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 112AN XY: 727212
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PON1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at