Genetic Variant NM_013326.5:c.65C>A (chr18-23503683-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 708242.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 352 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013326.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMC1	NM_013326.5	MANE Select	c.65C>A	p.Pro22His	missense	Exon 1 of 20	NP_037458.3
RMC1	NM_001318707.1		c.-178C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001305636.1	Q96DM3
RMC1	NM_001318708.1		c.-322C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001305637.1	B7Z2Y1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMC1	ENST00000269221.8	TSL:1 MANE Select	c.65C>A	p.Pro22His	missense	Exon 1 of 20	ENSP00000269221.2	Q96DM3
RMC1	ENST00000590868.5	TSL:2	c.65C>A	p.Pro22His	missense	Exon 1 of 18	ENSP00000467007.1	K7ENL9
RMC1	ENST00000615148.5	TSL:5	c.65C>A	p.Pro22His	missense	Exon 1 of 20	ENSP00000482573.2	A0A087WZD4

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

GnomAD2 exomes

AF:

0.00223

AC:

526

AN:

236056

AF XY:

0.00217

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 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

African (AFR)

AF:

0.000588

AC:

AN:

30630

American (AMR)

AF:

0.00139

AC:

AN:

43160

Ashkenazi Jewish (ASJ)

AF:

0.00511

AC:

130

AN:

25442

East Asian (EAS)

AF:

0.00

AC:

AN:

37300

South Asian (SAS)

AF:

0.000897

AC:

AN:

84722

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00228

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00339

AC:

3735

AN:

1102864

Other (OTH)

AF:

0.00261

AC:

155

AN:

59290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

222

444

665

887

1109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152128

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41540

American (AMR)

AF:

0.00294

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000945

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00364

AC:

247

AN:

67944

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00296

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0074

MetaSVM

Benign

-1.1

PhyloP100

4.2

PROVEAN

Benign

-0.82

REVEL

Benign

0.040

Sift

Benign

0.11

Sift4G

Benign

0.10

Polyphen

0.76

Vest4

0.45

MVP

0.10

MPC

0.57

ClinPred

0.010

GERP RS

3.7

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.31

gMVP

0.14

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over