2-21043879-CCAG-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM2PM4_SupportingBP6_Very_Strong
The NM_000384.3(APOB):βc.64_66delβ(p.Leu22del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,176,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (β β ). Synonymous variant affecting the same amino acid position (i.e. L22L) has been classified as Likely benign.
Frequency
Consequence
NM_000384.3 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.64_66del | p.Leu22del | inframe_deletion | 1/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.64_66del | p.Leu22del | inframe_deletion | 1/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000399256.4 | c.64_66del | p.Leu22del | inframe_deletion | 1/17 | 1 | |||
APOB | ENST00000673739.2 | c.64_66del | p.Leu22del | inframe_deletion, NMD_transcript_variant | 1/25 | ||||
APOB | ENST00000673882.2 | c.64_66del | p.Leu22del | inframe_deletion, NMD_transcript_variant | 1/23 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 6AN: 150460Hom.: 0 Cov.: 31 FAILED QC
GnomAD4 exome AF: 0.00200 AC: 2349AN: 1176340Hom.: 0 AF XY: 0.00231 AC XY: 1342AN XY: 580032
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000399 AC: 6AN: 150460Hom.: 0 Cov.: 31 AF XY: 0.0000408 AC XY: 3AN XY: 73440
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 22, 2019 | 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. - |
Familial hypercholesterolemia Benign:1
Benign, criteria provided, single submitter | clinical testing | GENinCode PLC | Feb 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at