rs3187907
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001101648.2(NPC1L1):c.*837A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,442 control chromosomes in the GnomAD database, including 1,913 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 0.14 ( 1910 hom., cov: 33)
Exomes 𝑓: 0.17 ( 3 hom. )
Consequence
NPC1L1
NM_001101648.2 3_prime_UTR
NM_001101648.2 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.444
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=-0.91).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPC1L1 | NM_001101648.2 | c.*837A>G | 3_prime_UTR_variant | 19/19 | ENST00000381160.8 | ||
NPC1L1 | NM_013389.3 | c.*837A>G | 3_prime_UTR_variant | 20/20 | |||
NPC1L1 | XM_011515326.4 | c.*837A>G | 3_prime_UTR_variant | 18/18 | |||
NPC1L1 | XM_011515328.3 | c.*837A>G | 3_prime_UTR_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPC1L1 | ENST00000381160.8 | c.*837A>G | 3_prime_UTR_variant | 19/19 | 1 | NM_001101648.2 | P1 | ||
NPC1L1 | ENST00000289547.8 | c.*837A>G | 3_prime_UTR_variant | 20/20 | 1 | ||||
NPC1L1 | ENST00000546276.5 | c.*837A>G | 3_prime_UTR_variant | 18/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.139 AC: 21119AN: 152168Hom.: 1910 Cov.: 33
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GnomAD4 exome AF: 0.167 AC: 26AN: 156Hom.: 3 Cov.: 0 AF XY: 0.170 AC XY: 15AN XY: 88
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GnomAD4 genome ? AF: 0.139 AC: 21115AN: 152286Hom.: 1910 Cov.: 33 AF XY: 0.136 AC XY: 10115AN XY: 74450
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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