rs150144164
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_000527.5(LDLR):āc.345C>Gā(p.Arg115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,444 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 Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. R115R) has been classified as Benign.
Frequency
Consequence
NM_000527.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.345C>G | p.Arg115= | synonymous_variant | 4/18 | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.345C>G | p.Arg115= | synonymous_variant | 4/18 | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000718 AC: 18AN: 250806Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135784
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461256Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 726954
GnomAD4 genome AF: 0.000164 AC: 25AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74344
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Oct 19, 2020 | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as likely benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hypercholesterolemia 1 (MIM#143890) and LDL cholesterol level QTL2 (MIM#143890). (I) 0107 - This gene is associated with autosomal dominant disease however compound heterozygotes and homozygotes have been reported (OMIM; PMID: 10978268). (I) 0200 - Variant is predicted to result in a synonymous change. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (25 heterozygotes, 0 homozygotes). (SP) 0506 - Abnormal splicing is not predicted and nucleotide is poorly conserved. (SB) 0600 - Variant is located in an annotated LDLa superfamily domain (NCBI, PDB). (I) 0705 - No comparable synonymous variants have previous evidence for pathogenicity. However, a different variant affecting the same nucleotide, c.345C>T (p.(Arg115=) has been reported by a research laboratory (ClinVar). (I) 0806 - This variant has moderate previous evidence of being benign in unrelated individuals. This variant has been reported as likely benign and benign in ClinVar. (SB) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
Familial hypercholesterolemia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 19, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 02, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at