GeneBe

rs3837910

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_000271.5(NPC1):​c.1947+13_1947+16delGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 937,566 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

NPC1
NM_000271.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.765
Variant links:
Genes affected
NPC1 (HGNC:7897): (NPC intracellular cholesterol transporter 1) This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 18-23544943-ACCCC-A is Benign according to our data. Variant chr18-23544943-ACCCC-A is described in Lovd as [Likely_benign]. Variant chr18-23544943-ACCCC-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPC1NM_000271.5 linkc.1947+13_1947+16delGGGG intron_variant Intron 12 of 24 ENST00000269228.10 NP_000262.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPC1ENST00000269228.10 linkc.1947+13_1947+16delGGGG intron_variant Intron 12 of 24 1 NM_000271.5 ENSP00000269228.4 O15118-1
NPC1ENST00000591051.1 linkc.1023+13_1023+16delGGGG intron_variant Intron 5 of 17 2 ENSP00000467636.1 K7EQ23
NPC1ENST00000540608.5 linkn.1861+13_1861+16delGGGG intron_variant Intron 10 of 15 2

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000533
AC:
5
AN:
937566
Hom.:
0
AF XY:
0.00000417
AC XY:
2
AN XY:
479080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000747
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-21124907; API