Variant chr18-23530033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_013326.5(RMC1):c.1500C>T(p.Tyr500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,613,348 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 60 hom. )

Consequence

RMC1
NM_013326.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

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

RMC1 links:

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]

NPC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 18-23530033-C-T is Benign according to our data. Variant chr18-23530033-C-T is described in ClinVar as [Benign]. Clinvar id is 781357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00653 (9542/1461044) while in subpopulation MID AF= 0.0246 (142/5766). AF 95% confidence interval is 0.0213. There are 60 homozygotes in gnomad4_exome. There are 5038 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 902 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMC1	NM_013326.5 linkuse as main transcript	c.1500C>T	p.Tyr500=	synonymous_variant	17/20	ENST00000269221.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMC1	ENST00000269221.8 linkuse as main transcript	c.1500C>T	p.Tyr500=	synonymous_variant	17/20	1	NM_013326.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00609

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00827

AC:

2080

AN:

251402

Hom.:

AF XY:

0.00896

AC XY:

1218

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.00718

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.00653

AC:

9542

AN:

1461044

Hom.:

Cov.:

AF XY:

0.00693

AC XY:

5038

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.00531

Gnomad4 OTH exome

AF:

0.00827

GnomAD4 genome

AF:

0.00592

AC:

902

AN:

152304

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

506

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0216

Gnomad4 NFE

AF:

0.00609

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00669

Hom.:

Bravo

AF:

0.00419

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00723

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.3

DANN

Benign

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over