chr19-11131312-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_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 Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.2579C>T | p.Ala860Val | missense_variant | 18/18 | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.2579C>T | p.Ala860Val | missense_variant | 18/18 | 1 | NM_000527.5 | P3 |
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 Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 07, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2021 | This sequence change replaces alanine with valine at codon 860 of the LDLR protein (p.Ala860Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs13306505, ExAC 0.08%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 18718593, 25487149, 30745271). This variant is also known as A839V. ClinVar contains an entry for this variant (Variation ID: 374957). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Benign, criteria provided, single submitter | clinical testing | Department of Molecular Innovation in Lipidology, National Cerebral & Cardiovascular Center Reseach Institute | Nov 20, 2018 | LDLR A860V variant is interpreted as a benign variant based on pedigree-based genetic analysis. - |
Hypercholesterolemia, familial, 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Robarts Research Institute, Western University | Jan 02, 2018 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Mar 30, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at