19-11110810-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000527.5(LDLR):c.1060+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,607,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
LDLR
NM_000527.5 intron
NM_000527.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.339
Genes affected
LDLR (HGNC:6547): (low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| LDLR | NM_000527.5 | c.1060+39C>T | intron_variant | ENST00000558518.6 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LDLR | ENST00000558518.6 | c.1060+39C>T | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246848Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133930
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GnomAD4 exome AF: 0.00000412 AC: 6AN: 1455350Hom.: 0 Cov.: 33 AF XY: 0.00000552 AC XY: 4AN XY: 724232
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GnomAD4 genome 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
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ClinVar
Not reported inComputational scores
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Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at