rs72653078
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000384.3(APOB):c.3712C>A(p.Leu1238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.3712C>A | p.Leu1238Ile | missense_variant | 24/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.3712C>A | p.Leu1238Ile | missense_variant | 24/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000673739.2 | c.*3018C>A | 3_prime_UTR_variant, NMD_transcript_variant | 23/25 | |||||
APOB | ENST00000673882.2 | c.*2807C>A | 3_prime_UTR_variant, NMD_transcript_variant | 22/23 |
Frequencies
GnomAD3 genomes ? AF: 0.000867 AC: 132AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000247 AC: 62AN: 251296Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135810
GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461786Hom.: 0 Cov.: 32 AF XY: 0.0000770 AC XY: 56AN XY: 727190
GnomAD4 genome ? AF: 0.000873 AC: 133AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.000833 AC XY: 62AN XY: 74470
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Familial hypobetalipoproteinemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at