rs774615547
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000527.5(LDLR):c.16_17insTTCCT(p.Trp6PhefsTer202) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,184 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign.
Frequency
Consequence
NM_000527.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.16_17insTTCCT | p.Trp6PhefsTer202 | frameshift_variant | 1/18 | ENST00000558518.6 | |
LDLR-AS1 | NR_163945.1 | n.97_98insGAAAG | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.16_17insTTCCT | p.Trp6PhefsTer202 | frameshift_variant | 1/18 | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248554Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135046
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460184Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726380
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Robarts Research Institute, Western University | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at