rs2074351
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000446.7(PON1):c.75-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,156,122 control chromosomes in the GnomAD database, including 49,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.26 ( 5592 hom., cov: 32)
Exomes 𝑓: 0.29 ( 44376 hom. )
Consequence
PON1
NM_000446.7 intron
NM_000446.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0630
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 7-95318487-G-A is Benign according to our data. Variant chr7-95318487-G-A is described in ClinVar as [Benign]. Clinvar id is 1288755.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PON1 | NM_000446.7 | c.75-94C>T | intron_variant | ENST00000222381.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PON1 | ENST00000222381.8 | c.75-94C>T | intron_variant | 1 | NM_000446.7 | P1 | |||
PON1 | ENST00000470502.1 | n.101C>T | non_coding_transcript_exon_variant | 1/4 | 4 | ||||
PON1 | ENST00000433729.1 | c.75-94C>T | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.263 AC: 39961AN: 151976Hom.: 5585 Cov.: 32
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GnomAD4 exome AF: 0.289 AC: 290159AN: 1004028Hom.: 44376 Cov.: 13 AF XY: 0.290 AC XY: 149711AN XY: 517118
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GnomAD4 genome ? AF: 0.263 AC: 39990AN: 152094Hom.: 5592 Cov.: 32 AF XY: 0.266 AC XY: 19779AN XY: 74352
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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