rs12720789
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000384.3(APOB):c.383+1054C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 152,252 control chromosomes in the GnomAD database, including 7 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 0.0048 ( 7 hom., cov: 33)
Consequence
APOB
NM_000384.3 intron
NM_000384.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.185
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00481 (733/152252) while in subpopulation AFR AF= 0.0165 (687/41550). AF 95% confidence interval is 0.0155. There are 7 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 7 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.383+1054C>T | intron_variant | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.383+1054C>T | intron_variant | 1 | NM_000384.3 | P1 | |||
APOB | ENST00000399256.4 | c.383+1054C>T | intron_variant | 1 | |||||
APOB | ENST00000673739.2 | c.383+1054C>T | intron_variant, NMD_transcript_variant | ||||||
APOB | ENST00000673882.2 | c.383+1054C>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00477 AC: 725AN: 152134Hom.: 7 Cov.: 33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00481 AC: 733AN: 152252Hom.: 7 Cov.: 33 AF XY: 0.00450 AC XY: 335AN XY: 74440
GnomAD4 genome
?
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733
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33
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335
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74440
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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