Variant chr18-23527835-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_013326.5(RMC1):c.1230C>G(p.Ala410Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,614,066 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 10 hom. )

Consequence

RMC1
NM_013326.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28

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:

RMC1 (HGNC:):

RMC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 18-23527835-C-G is Benign according to our data. Variant chr18-23527835-C-G is described in ClinVar as [Benign]. Clinvar id is 778149.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BS2

High AC in GnomAd4 at 315 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMC1	NM_013326.5 linkuse as main transcript	c.1230C>G	p.Ala410Ala	synonymous_variant	14/20	ENST00000269221.8	NP_037458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RMC1	ENST00000269221.8 linkuse as main transcript	c.1230C>G	p.Ala410Ala	synonymous_variant	14/20	1	NM_013326.5	ENSP00000269221.2	Q96DM3
RMC1	ENST00000590868.5 linkuse as main transcript	c.1086C>G	p.Ala362Ala	synonymous_variant	12/18	2		ENSP00000467007.1	K7ENL9
RMC1	ENST00000615148.5 linkuse as main transcript	c.1230C>G	p.Ala410Ala	synonymous_variant	14/20	5		ENSP00000482573.2	A0A087WZD4
RMC1	ENST00000589215.5 linkuse as main transcript	n.*887C>G		non_coding_transcript_exon_variant	13/19	2		ENSP00000467852.1	K7EQJ3
RMC1	ENST00000589215.5 linkuse as main transcript	n.*887C>G		3_prime_UTR_variant	13/19	2		ENSP00000467852.1	K7EQJ3

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

315

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00218

AC:

549

AN:

251420

Hom.:

AF XY:

0.00197

AC XY:

268

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00228

AC:

3339

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1603

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152248

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0152

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000854

EpiCase

AF:

0.00202

EpiControl

AF:

0.00202

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

Labcorp Genetics (formerly Invitae), Labcorp

Jun 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.74

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