rs55792959
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP4
This summary comes from the ClinGen Evidence Repository: The NM_000527.5(LDLR):c.941-39C>T variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes BA1 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1: FAF=0.005249 (0.5249%) in European (Non-Finnish) exomes (gnomAD v2.1.1). So BA1 is met.BP4: The variant is not predicted to affect the splicing process by SpliceAI. So, BP4 is met. LINK:https://erepo.genome.network/evrepo/ui/classification/CA030745/MONDO:0007750/013
Frequency
Consequence
NM_000527.5 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.941-39C>T | intron_variant | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.941-39C>T | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00410 AC: 623AN: 152080Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00364 AC: 908AN: 249520Hom.: 5 AF XY: 0.00384 AC XY: 519AN XY: 135180
GnomAD4 exome AF: 0.00561 AC: 8191AN: 1459876Hom.: 32 Cov.: 31 AF XY: 0.00558 AC XY: 4049AN XY: 726214
GnomAD4 genome ? AF: 0.00409 AC: 623AN: 152198Hom.: 1 Cov.: 32 AF XY: 0.00376 AC XY: 280AN XY: 74406
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Uncertain:3Benign:3
Uncertain significance, criteria provided, single submitter | research | Iberoamerican FH Network | Mar 01, 2016 | - - |
Likely benign, criteria provided, single submitter | literature only | LDLR-LOVD, British Heart Foundation | Mar 25, 2016 | - - |
Benign, no assertion criteria provided | research | Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum | - | - - |
Uncertain significance, criteria provided, single submitter | research | Fundacion Hipercolesterolemia Familiar | Mar 01, 2016 | - - |
Uncertain significance, criteria provided, single submitter | research | Laboratory of Genetics and Molecular Cardiology, University of São Paulo | Mar 01, 2016 | - - |
Benign, reviewed by expert panel | curation | ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel | Apr 28, 2023 | The NM_000527.5(LDLR):c.941-39C>T variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes BA1 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: BA1: FAF=0.005249 (0.5249%) in European (Non-Finnish) exomes (gnomAD v2.1.1). So BA1 is met. BP4: The variant is not predicted to affect the splicing process by SpliceAI. So, BP4 is met. - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2018 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | LDLR: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Familial hypercholesterolemia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 06, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at