18-23544950-C-CCCCCCG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_000271.5(NPC1):​c.1947+9_1947+10insCGGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,415,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

NPC1
NM_000271.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.825
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 18-23544950-C-CCCCCCG is Benign according to our data. Variant chr18-23544950-C-CCCCCCG is described in ClinVar as [Likely_benign]. Clinvar id is 3022777.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NPC1NM_000271.5 linkc.1947+9_1947+10insCGGGGG intron_variant ENST00000269228.10 NP_000262.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NPC1ENST00000269228.10 linkc.1947+9_1947+10insCGGGGG intron_variant 1 NM_000271.5 ENSP00000269228.4 O15118-1
NPC1ENST00000591051.1 linkc.1023+9_1023+10insCGGGGG intron_variant 2 ENSP00000467636.1 K7EQ23
NPC1ENST00000540608.5 linkn.1861+9_1861+10insCGGGGG intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000696
AC:
1
AN:
143688
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000158
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000157
AC:
2
AN:
1272186
Hom.:
0
Cov.:
26
AF XY:
0.00000312
AC XY:
2
AN XY:
640102
show subpopulations
Gnomad4 AFR exome
AF:
0.0000320
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:
0.00
Gnomad4 OTH exome
AF:
0.0000187
GnomAD4 genome
AF:
0.00000696
AC:
1
AN:
143688
Hom.:
0
Cov.:
27
AF XY:
0.0000142
AC XY:
1
AN XY:
70232
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000158
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Niemann-Pick disease, type C1 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs772150994; hg19: chr18-21124914; API