rs749322464
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_000527.5(LDLR):āc.1080T>Gā(p.Asp360Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D360H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000527.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.1080T>G | p.Asp360Glu | missense_variant | 8/18 | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.1080T>G | p.Asp360Glu | missense_variant | 8/18 | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251312Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461422Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727036
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74336
ClinVar
Submissions by phenotype
Familial hypercholesterolemia Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 360 of the LDLR protein (p.Asp360Glu). This variant is present in population databases (rs749322464, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 440624). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 04, 2023 | This missense variant (also known as p.Asp339Glu in the mature protein) replaces aspartic acid with glutamic acid at codon 360 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has been identified in 3/251312 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. - |
Hypercholesterolemia, familial, 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 30, 2023 | This missense variant (also known as p.Asp339Glu in the mature protein) replaces aspartic acid with glutamic acid at codon 360 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has been identified in 3/251312 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. - |
Benign, no assertion criteria provided | research | Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at