Variant 18-23503683-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013326.5(RMC1):c.65C>A(p.Pro22His) variant causes a missense change. The variant allele was found at a frequency of 0.00288 in 1,594,282 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 5 hom. )

Consequence

RMC1
NM_013326.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007394731).

BP6

Variant 18-23503683-C-A is Benign according to our data. Variant chr18-23503683-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 708242.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 352 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMC1	NM_013326.5 linkuse as main transcript	c.65C>A	p.Pro22His	missense_variant	1/20	ENST00000269221.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMC1	ENST00000269221.8 linkuse as main transcript	c.65C>A	p.Pro22His	missense_variant	1/20	1	NM_013326.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

352

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00223

AC:

526

AN:

236056

Hom.:

AF XY:

0.00217

AC XY:

280

AN XY:

128812

show subpopulations

Gnomad AFR exome

AF:

0.000451

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00624

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000650

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00336

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00294

AC:

4247

AN:

1442154

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

2077

AN XY:

717708

show subpopulations

Gnomad4 AFR exome

AF:

0.000588

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00511

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000897

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.00339

Gnomad4 OTH exome

AF:

0.00261

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152128

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00364

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.00220

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00228

AC:

276

Asia WGS

AF:

0.000290

AC:

AN:

3462

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

Aug 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.015

T;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.89

D;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.76

.;P;.

Vest4

0.45

MVP

0.10

MPC

0.57

ClinPred

0.010

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.31

gMVP

0.14

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