19-11131312-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BS1BS2_Supporting
The NM_000527.5(LDLR):c.2579C>T(p.Ala860Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,126 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A860A) has been classified as Likely benign.
Frequency
Consequence
NM_000527.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.2579C>T | p.Ala860Val | missense_variant | Exon 18 of 18 | ENST00000558518.6 | NP_000518.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251488Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135918
GnomAD4 exome AF: 0.000171 AC: 250AN: 1461826Hom.: 2 Cov.: 34 AF XY: 0.000146 AC XY: 106AN XY: 727222
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74464
ClinVar
Submissions by phenotype
Familial hypercholesterolemia Benign:3
LDLR A860V variant is interpreted as a benign variant based on pedigree-based genetic analysis. -
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Hypercholesterolemia, familial, 1 Uncertain:2
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not provided Uncertain:1
Observed in individuals with familial hypercholesterolemia (PMID: 18718593, 34176852, 35480308); Segregation studies in two families with the p.(A860V) and another LDLR variant, suggest that the p.(A860V) is likely not segregating with the disease in these families (Hori et al., 2019); these findings suggest that p.(A860V) is a benign variant (PMID: 30745271); In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as p.(A839V); This variant is associated with the following publications: (PMID: 26332594, 25487149, 34176852, 18718593, 33020668, 31491741, 35480308, 30745271) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at