rs758901876
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000527.5(LDLR):c.190+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,603,778 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
LDLR
NM_000527.5 intron
NM_000527.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.13
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 -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 19-11100379-T-C is Benign according to our data. Variant chr19-11100379-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 251052.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11100379-T-C is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.190+34T>C | intron_variant | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.190+34T>C | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246650Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133746
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GnomAD4 exome AF: 0.0000193 AC: 28AN: 1451602Hom.: 0 Cov.: 28 AF XY: 0.0000208 AC XY: 15AN XY: 722632
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74336
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Benign:1
Likely benign, criteria provided, single submitter | literature only | LDLR-LOVD, British Heart Foundation | Mar 25, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at