rs1270618112
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NR_163945.1(LDLR-AS1):n.302_304del variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000758 in 395,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
LDLR-AS1
NR_163945.1 non_coding_transcript_exon
NR_163945.1 non_coding_transcript_exon
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.66
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR-AS1 | NR_163945.1 | n.302_304del | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000758 AC: 3AN: 395754Hom.: 0 AF XY: 0.00000482 AC XY: 1AN XY: 207338
GnomAD4 exome
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3
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395754
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1
AN XY:
207338
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Pathogenic:1Uncertain:2
Uncertain significance, criteria provided, single submitter | curation;literature only | Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge | Mar 01, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Pathogenic, no assertion criteria provided | research | Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum | - | - - |
Familial hypercholesterolemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2021 | This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 9610768). This variant is also known as -92 (FH-Pedi-2). ClinVar contains an entry for this variant (Variation ID: 438314). Studies have shown that this variant alters LDLR gene expression (PMID: 9610768). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at