Variant rs55837134 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Variant links:

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]

NPC1L1 links:

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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 linkuse as main transcript	c.2547+22C>T		intron_variant		ENST00000381160.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NPC1L1	ENST00000381160.8 linkuse as main transcript	c.2547+22C>T	intron_variant	1	NM_001101648.2	P1
NPC1L1	ENST00000289547.8 linkuse as main transcript	c.2547+22C>T	intron_variant	1			Q9UHC9-1
NPC1L1	ENST00000546276.5 linkuse as main transcript	c.2547+22C>T	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18933

AN:

152066

Hom.:

1579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.0768

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.133

AC:

33270

AN:

250816

Hom.:

2881

AF XY:

0.135

AC XY:

18385

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.0641

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.159

AC:

231679

AN:

1461700

Hom.:

19955

Cov.:

AF XY:

0.158

AC XY:

114539

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.0671

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.00335

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.124

AC:

18926

AN:

152184

Hom.:

1580

Cov.:

AF XY:

0.125

AC XY:

9325

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0411

Gnomad4 AMR

AF:

0.0766

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.00541

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.116

Hom.:

245

Bravo

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.079

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over