19-11128126-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000527.5(LDLR):c.2389+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000676 in 1,575,942 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00033 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00071 ( 17 hom. )
Consequence
LDLR
NM_000527.5 intron
NM_000527.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.04
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 19-11128126-C-T is Benign according to our data. Variant chr19-11128126-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1712915.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 17 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.2389+41C>T | intron_variant | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.2389+41C>T | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152140Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.00140 AC: 351AN: 250664Hom.: 6 AF XY: 0.00178 AC XY: 241AN XY: 135614
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GnomAD4 exome AF: 0.000713 AC: 1015AN: 1423684Hom.: 17 Cov.: 27 AF XY: 0.000970 AC XY: 689AN XY: 710398
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GnomAD4 genome AF: 0.000335 AC: 51AN: 152258Hom.: 1 Cov.: 31 AF XY: 0.000510 AC XY: 38AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at