18-23516432-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_013326.5(RMC1):c.653+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,611,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
RMC1
NM_013326.5 intron
NM_013326.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.524
Genes affected
RMC1 (HGNC:24326): (regulator of MON1-CCZ1) This gene encodes a colon cancer associated protein. [provided by RefSeq, Jan 2013]
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 18-23516432-G-A is Benign according to our data. Variant chr18-23516432-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 734642.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RMC1 | NM_013326.5 | c.653+9G>A | intron_variant | ENST00000269221.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RMC1 | ENST00000269221.8 | c.653+9G>A | intron_variant | 1 | NM_013326.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251384Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135866
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GnomAD4 exome AF: 0.0000288 AC: 42AN: 1459324Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21AN XY: 726106
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2018 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at