2-21033533-G-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000384.3(APOB):c.905-15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,603,126 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000384.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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APOB | ENST00000233242.5 | c.905-15C>G | intron_variant | Intron 8 of 28 | 1 | NM_000384.3 | ENSP00000233242.1 | |||
APOB | ENST00000399256.4 | c.905-15C>G | intron_variant | Intron 8 of 16 | 1 | ENSP00000382200.4 | ||||
APOB | ENST00000673739.2 | n.*211-15C>G | intron_variant | Intron 7 of 24 | ENSP00000501110.2 | |||||
APOB | ENST00000673882.2 | n.*211-15C>G | intron_variant | Intron 7 of 22 | ENSP00000501253.2 |
Frequencies
GnomAD3 genomes AF: 0.00337 AC: 513AN: 152176Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00322 AC: 809AN: 251376Hom.: 3 AF XY: 0.00324 AC XY: 440AN XY: 135858
GnomAD4 exome AF: 0.00391 AC: 5673AN: 1450832Hom.: 13 Cov.: 29 AF XY: 0.00389 AC XY: 2814AN XY: 722510
GnomAD4 genome AF: 0.00337 AC: 513AN: 152294Hom.: 3 Cov.: 32 AF XY: 0.00334 AC XY: 249AN XY: 74456
ClinVar
Submissions by phenotype
not provided Benign:3
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APOB: BS2 -
Hypercholesterolemia, familial, 1 Uncertain:1Benign:1
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not specified Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Familial hypobetalipoproteinemia 1 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
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Hypercholesterolemia, autosomal dominant, type B Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
APOB-related disorder Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at