rs12714214
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000384.3(APOB):c.1661C>T(p.Pro554Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000497 in 1,613,704 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P554R) has been classified as Likely benign.
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.1661C>T | p.Pro554Leu | missense_variant | 13/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.1661C>T | p.Pro554Leu | missense_variant | 13/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000399256.4 | c.1661C>T | p.Pro554Leu | missense_variant | 13/17 | 1 | |||
APOB | ENST00000673739.2 | c.*967C>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/25 | |||||
APOB | ENST00000673882.2 | c.*967C>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/23 |
Frequencies
GnomAD3 genomes AF: 0.00262 AC: 398AN: 152138Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.000681 AC: 171AN: 251160Hom.: 1 AF XY: 0.000501 AC XY: 68AN XY: 135764
GnomAD4 exome AF: 0.000276 AC: 404AN: 1461448Hom.: 2 Cov.: 32 AF XY: 0.000256 AC XY: 186AN XY: 727034
GnomAD4 genome AF: 0.00261 AC: 398AN: 152256Hom.: 4 Cov.: 33 AF XY: 0.00265 AC XY: 197AN XY: 74446
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 20, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 04, 2023 | - - |
Hypercholesterolemia, familial, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Laboratory of Genetics and Molecular Cardiology, University of São Paulo | Mar 01, 2016 | - - |
Familial hypobetalipoproteinemia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Aug 30, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Hypercholesterolemia, autosomal dominant, type B Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Aug 30, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 30, 2019 | This alteration is classified as likely 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. - |
Familial hypercholesterolemia Benign:1
Benign, criteria provided, single submitter | clinical testing | GENinCode PLC | Jun 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at