rs12714224
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The ENST00000233242.5(APOB):c.1352+60C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,439,188 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0078 ( 9 hom., cov: 33)
Exomes 𝑓: 0.0035 ( 30 hom. )
Consequence
APOB
ENST00000233242.5 intron
ENST00000233242.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0350
Genes affected
APOB (HGNC:603): (apolipoprotein B) This gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels. [provided by RefSeq, Dec 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00779 (1187/152328) while in subpopulation AFR AF= 0.0161 (671/41572). AF 95% confidence interval is 0.0151. There are 9 homozygotes in gnomad4. There are 587 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 9 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.1352+60C>A | intron_variant | ENST00000233242.5 | NP_000375.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.1352+60C>A | intron_variant | 1 | NM_000384.3 | ENSP00000233242 | P1 | |||
APOB | ENST00000399256.4 | c.1352+60C>A | intron_variant | 1 | ENSP00000382200 | |||||
APOB | ENST00000673739.2 | c.*658+60C>A | intron_variant, NMD_transcript_variant | ENSP00000501110 | ||||||
APOB | ENST00000673882.2 | c.*658+60C>A | intron_variant, NMD_transcript_variant | ENSP00000501253 |
Frequencies
GnomAD3 genomes AF: 0.00781 AC: 1189AN: 152210Hom.: 8 Cov.: 33
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GnomAD4 exome AF: 0.00355 AC: 4562AN: 1286860Hom.: 30 AF XY: 0.00365 AC XY: 2370AN XY: 649324
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GnomAD4 genome AF: 0.00779 AC: 1187AN: 152328Hom.: 9 Cov.: 33 AF XY: 0.00788 AC XY: 587AN XY: 74488
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge | Mar 01, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
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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