rs55837134
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001101648.2(NPC1L1):c.2547+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,884 control chromosomes in the GnomAD database, including 21,535 homozygotes. 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 0.12 ( 1580 hom., cov: 32)
Exomes 𝑓: 0.16 ( 19955 hom. )
Consequence
NPC1L1
NM_001101648.2 intron
NM_001101648.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.23
Genes affected
NPC1L1 (HGNC:7898): (NPC1 like intracellular cholesterol transporter 1) The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPC1L1 | NM_001101648.2 | c.2547+22C>T | intron_variant | ENST00000381160.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPC1L1 | ENST00000381160.8 | c.2547+22C>T | intron_variant | 1 | NM_001101648.2 | P1 | |||
NPC1L1 | ENST00000289547.8 | c.2547+22C>T | intron_variant | 1 | |||||
NPC1L1 | ENST00000546276.5 | c.2547+22C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.125 AC: 18933AN: 152066Hom.: 1579 Cov.: 32
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GnomAD3 exomes AF: 0.133 AC: 33270AN: 250816Hom.: 2881 AF XY: 0.135 AC XY: 18385AN XY: 135722
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GnomAD4 exome AF: 0.159 AC: 231679AN: 1461700Hom.: 19955 Cov.: 34 AF XY: 0.158 AC XY: 114539AN XY: 727162
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GnomAD4 genome ? AF: 0.124 AC: 18926AN: 152184Hom.: 1580 Cov.: 32 AF XY: 0.125 AC XY: 9325AN XY: 74424
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
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