rs5128
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000227667.8(APOC3):c.*40G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,612,872 control chromosomes in the GnomAD database, including 630,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.86 ( 56779 hom., cov: 33)
Exomes 𝑓: 0.88 ( 573988 hom. )
Consequence
APOC3
ENST00000227667.8 3_prime_UTR
ENST00000227667.8 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.16
Genes affected
APOC3 (HGNC:610): (apolipoprotein C3) This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 11-116832924-G-C is Benign according to our data. Variant chr11-116832924-G-C is described in ClinVar as [Benign]. Clinvar id is 1250845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116832924-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOC3 | NM_000040.3 | c.*40G>C | 3_prime_UTR_variant | 4/4 | ENST00000227667.8 | NP_000031.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOC3 | ENST00000227667.8 | c.*40G>C | 3_prime_UTR_variant | 4/4 | 1 | NM_000040.3 | ENSP00000227667 | P1 | ||
APOC3 | ENST00000630701.1 | c.*40G>C | 3_prime_UTR_variant | 3/3 | 1 | ENSP00000486182 | ||||
APOC3 | ENST00000375345.3 | c.*40G>C | 3_prime_UTR_variant | 4/4 | 5 | ENSP00000364494 |
Frequencies
GnomAD3 genomes AF: 0.862 AC: 131089AN: 152120Hom.: 56755 Cov.: 33
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GnomAD3 exomes AF: 0.839 AC: 210515AN: 250898Hom.: 89243 AF XY: 0.836 AC XY: 113526AN XY: 135734
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GnomAD4 exome AF: 0.884 AC: 1290860AN: 1460634Hom.: 573988 Cov.: 48 AF XY: 0.878 AC XY: 638016AN XY: 726638
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GnomAD4 genome AF: 0.862 AC: 131167AN: 152238Hom.: 56779 Cov.: 33 AF XY: 0.854 AC XY: 63577AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2018 | This variant is associated with the following publications: (PMID: 27624799, 15100713, 19034316) - |
Myocardial infarction, susceptibility to Uncertain:1
Uncertain significance, no assertion criteria provided | reference population | iDNA Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at