2-21043856-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000384.3(APOB):c.82+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 1,368,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000384.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.82+8C>A | splice_region_variant, intron_variant | 1 | NM_000384.3 | ENSP00000233242.1 | ||||
APOB | ENST00000399256.4 | c.82+8C>A | splice_region_variant, intron_variant | 1 | ENSP00000382200.4 | |||||
APOB | ENST00000673739.2 | n.82+8C>A | splice_region_variant, intron_variant | ENSP00000501110.2 | ||||||
APOB | ENST00000673882.2 | n.82+8C>A | splice_region_variant, intron_variant | ENSP00000501253.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.0000263 AC: 36AN: 1368674Hom.: 0 Cov.: 31 AF XY: 0.0000237 AC XY: 16AN XY: 675452
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 08, 2023 | To the best of our knowledge, this variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect APOB mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. - |
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at