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).
Frequency
Consequence
NM_000527.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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. -
- -
- -
Hypercholesterolemia, familial, 1 Uncertain:2
- -
- -
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