2-21043879-CCAGCAGCAG-CCAGCAGCAGCAGCAG
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_000384.3(APOB):c.61_66dupCTGCTG(p.Leu21_Leu22dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,416,518 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000384.3 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.61_66dupCTGCTG | p.Leu21_Leu22dup | conservative_inframe_insertion | Exon 1 of 29 | 1 | NM_000384.3 | ENSP00000233242.1 | ||
APOB | ENST00000399256.4 | c.61_66dupCTGCTG | p.Leu21_Leu22dup | conservative_inframe_insertion | Exon 1 of 17 | 1 | ENSP00000382200.4 | |||
APOB | ENST00000673739.2 | n.61_66dupCTGCTG | non_coding_transcript_exon_variant | Exon 1 of 25 | ENSP00000501110.2 | |||||
APOB | ENST00000673882.2 | n.61_66dupCTGCTG | non_coding_transcript_exon_variant | Exon 1 of 23 | ENSP00000501253.2 |
Frequencies
GnomAD3 genomes AF: 0.00133 AC: 200AN: 150590Hom.: 2 Cov.: 31
GnomAD3 exomes AF: 0.00337 AC: 248AN: 73646Hom.: 2 AF XY: 0.00191 AC XY: 80AN XY: 41836
GnomAD4 exome AF: 0.000621 AC: 786AN: 1265826Hom.: 17 Cov.: 31 AF XY: 0.000509 AC XY: 318AN XY: 624992
GnomAD4 genome AF: 0.00132 AC: 199AN: 150692Hom.: 2 Cov.: 31 AF XY: 0.00134 AC XY: 99AN XY: 73630
ClinVar
Submissions by phenotype
not provided Benign:4
- -
- -
- -
APOB: BS1, BS2 -
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
- -
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). -
Cardiovascular phenotype Benign:1
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
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at