rs879254830
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_000527.5(LDLR):c.1207_1209del(p.Phe403del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L401L) has been classified as Likely benign.
Frequency
Consequence
NM_000527.5 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.1207_1209del | p.Phe403del | inframe_deletion | 9/18 | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.1207_1209del | p.Phe403del | inframe_deletion | 9/18 | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460964Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726802
GnomAD4 genome ? Cov.: 29
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Pathogenic:3Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix | Dec 16, 2016 | subject mutated among 2600 FH index cases screened = 1 - |
Uncertain significance, criteria provided, single submitter | literature only | LDLR-LOVD, British Heart Foundation | Mar 25, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation | Nov 05, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II | May 24, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at