chr19-11113370-A-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000527.5(LDLR):c.1279A>C(p.Arg427=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000595 in 1,613,792 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R427R) has been classified as Likely benign.
Frequency
Consequence
NM_000527.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.1279A>C | p.Arg427= | synonymous_variant | 9/18 | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.1279A>C | p.Arg427= | synonymous_variant | 9/18 | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152072Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251306Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135894
GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461720Hom.: 0 Cov.: 33 AF XY: 0.0000564 AC XY: 41AN XY: 727162
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152072Hom.: 0 Cov.: 29 AF XY: 0.0000404 AC XY: 3AN XY: 74290
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | literature only | LDLR-LOVD, British Heart Foundation | Mar 25, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Uncertain significance, criteria provided, single submitter | research | Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge | Mar 01, 2016 | 0/208 non-FH alleles - |
Familial hypercholesterolemia Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 17, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2022 | 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