rs6413503
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_000527.5(LDLR):c.2548-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,595,554 control chromosomes in the GnomAD database, including 928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.049 ( 433 hom., cov: 32)
Exomes 𝑓: 0.016 ( 495 hom. )
Consequence
LDLR
NM_000527.5 intron
NM_000527.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.25
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 19-11131228-G-A is Benign according to our data. Variant chr19-11131228-G-A is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.2548-53G>A | intron_variant | ENST00000558518.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.2548-53G>A | intron_variant | 1 | NM_000527.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0486 AC: 7398AN: 152142Hom.: 430 Cov.: 32
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GnomAD4 exome AF: 0.0163 AC: 23492AN: 1443294Hom.: 495 AF XY: 0.0157 AC XY: 11299AN XY: 719134
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GnomAD4 genome ? AF: 0.0487 AC: 7417AN: 152260Hom.: 433 Cov.: 32 AF XY: 0.0489 AC XY: 3641AN XY: 74448
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at