rs879254365
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5
The NR_163945.1(LDLR-AS1):n.265_266delinsAGGAGTTTGCAGAA variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
LDLR-AS1
NR_163945.1 non_coding_transcript_exon
NR_163945.1 non_coding_transcript_exon
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.33
Genes affected
LDLR (HGNC:6547): (low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP5
?
Variant 19-11089394-AC-TTCTGCAAACTCCT is Pathogenic according to our data. Variant chr19-11089394-AC-TTCTGCAAACTCCT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 250943.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR-AS1 | NR_163945.1 | n.265_266delinsAGGAGTTTGCAGAA | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000559340.2 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Fundacion Hipercolesterolemia Familiar | Mar 01, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | literature only | LDLR-LOVD, British Heart Foundation | Mar 25, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at