rs757215027

Variant names:

• chr18-23531716-GTTTT-G
• NM_000271.5:c.*482_*485delAAAA

Your query was ambiguous. Multiple possible variants found:

• chr18-23531716-GTTTT-G
• chr18-23531716-GTTTT-GTTT
• chr18-23531716-GTTTT-GTTTTT
• chr18-23531716-GTTTT-GTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000271.5(NPC1):​c.*482_*485delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPC1 NM_000271.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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]

RMC1 (HGNC:24326): (regulator of MON1-CCZ1) This gene encodes a colon cancer associated protein. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPC1	NM_000271.5	c.*482_*485delAAAA		3_prime_UTR_variant	Exon 25 of 25	ENST00000269228.10	NP_000262.2
RMC1	NM_013326.5	c.*16_*19delTTTT		3_prime_UTR_variant	Exon 20 of 20	ENST00000269221.8	NP_037458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPC1	ENST00000269228	c.*482_*485delAAAA		3_prime_UTR_variant	Exon 25 of 25	1	NM_000271.5	ENSP00000269228.4
RMC1	ENST00000269221.8	c.*16_*19delTTTT		3_prime_UTR_variant	Exon 20 of 20	1	NM_013326.5	ENSP00000269221.2
RMC1	ENST00000590868.5	c.*16_*19delTTTT		3_prime_UTR_variant	Exon 18 of 18	2		ENSP00000467007.1
RMC1	ENST00000615148.5	c.*36_*39delTTTT		3_prime_UTR_variant	Exon 20 of 20	5		ENSP00000482573.2
RMC1	ENST00000589215.5	n.*1523_*1526delTTTT		non_coding_transcript_exon_variant	Exon 19 of 19	2		ENSP00000467852.1
RMC1	ENST00000589215.5	n.*1523_*1526delTTTT		3_prime_UTR_variant	Exon 19 of 19	2		ENSP00000467852.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: chr18-21111680;