rs763282380
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000527.5(LDLR):c.-23A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,609,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000527.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.-23A>C | 5_prime_UTR_variant | Exon 1 of 18 | ENST00000558518.6 | NP_000518.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248266Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134804
GnomAD4 exome AF: 0.0000357 AC: 52AN: 1457612Hom.: 0 Cov.: 30 AF XY: 0.0000317 AC XY: 23AN XY: 725110
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Uncertain:2
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not provided Uncertain:1
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Familial hypercholesterolemia Uncertain:1
This variant is located in the 5' untranslated region of the LDLR gene. An in-vitro functional study has shown that this variant may not affect LDLR promoter activity (PMID: 31395865). This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 15241806). This variant has been identified in 3/279652 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at