19-11107550-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000527.5(LDLR):c.940+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 1,597,708 control chromosomes in the GnomAD database, including 2,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.039 ( 174 hom., cov: 31)
Exomes 𝑓: 0.050 ( 2112 hom. )
Consequence
LDLR
NM_000527.5 intron
NM_000527.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.271
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 19-11107550-G-A is Benign according to our data. Variant chr19-11107550-G-A is described in ClinVar as [Benign]. Clinvar id is 523739.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11107550-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.940+36G>A | intron_variant | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.940+36G>A | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0391 AC: 5946AN: 152026Hom.: 172 Cov.: 31
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GnomAD3 exomes AF: 0.0557 AC: 13895AN: 249668Hom.: 484 AF XY: 0.0576 AC XY: 7773AN XY: 134966
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GnomAD4 exome AF: 0.0496 AC: 71669AN: 1445564Hom.: 2112 Cov.: 32 AF XY: 0.0514 AC XY: 36978AN XY: 719114
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GnomAD4 genome AF: 0.0391 AC: 5948AN: 152144Hom.: 174 Cov.: 31 AF XY: 0.0404 AC XY: 3004AN XY: 74358
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Benign, no assertion criteria provided | research | Iberoamerican FH Network | Mar 01, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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