18-23503683-C-A

Variant names:

• chr18-23503683-C-A
• rs112277818
• NM_013326.5:c.65C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.21
• Publications: 5 publications found

Genes affected

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

ACMG classification

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 id is 708242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 352 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMC1	NM_013326.5	c.65C>A	p.Pro22His	missense_variant	Exon 1 of 20	ENST00000269221.8	NP_037458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMC1	ENST00000269221.8	c.65C>A	p.Pro22His	missense_variant	Exon 1 of 20	1	NM_013326.5	ENSP00000269221.2
RMC1	ENST00000590868.5	c.65C>A	p.Pro22His	missense_variant	Exon 1 of 18	2		ENSP00000467007.1
RMC1	ENST00000615148.5	c.65C>A	p.Pro22His	missense_variant	Exon 1 of 20	5		ENSP00000482573.2
RMC1	ENST00000589215.5	n.65C>A		non_coding_transcript_exon_variant	Exon 1 of 19	2		ENSP00000467852.1

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 352 AN: 152020 Hom.: 0 Cov.: 33

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

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.: 5 Cov.: 31 AF XY: 0.00289 AC XY: 2077 AN XY: 717708

African (AFR) AF: 0.000588 AC: 18 AN: 30630

American (AMR) AF: 0.00139 AC: 60 AN: 43160

Ashkenazi Jewish (ASJ) AF: 0.00511 AC: 130 AN: 25442

East Asian (EAS) AF: 0.00 AC: 0 AN: 37300

South Asian (SAS) AF: 0.000897 AC: 76 AN: 84722

European-Finnish (FIN) AF: 0.00113 AC: 60 AN: 53056

Middle Eastern (MID) AF: 0.00228 AC: 13 AN: 5690

European-Non Finnish (NFE) AF: 0.00339 AC: 3735 AN: 1102864

Other (OTH) AF: 0.00261 AC: 155 AN: 59290

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.00222 AC XY: 165 AN XY: 74384

African (AFR) AF: 0.000650 AC: 27 AN: 41540

American (AMR) AF: 0.00294 AC: 45 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.000945 AC: 10 AN: 10584

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00364 AC: 247 AN: 67944

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00296 Hom.: 4

Bravo AF: 0.00220

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00228 AC: 276

Asia WGS AF: 0.000290 AC: 1 AN: 3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.0074	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		4.2
PROVEAN	Benign	-0.82	.;N;.
REVEL	Benign	0.040
Sift	Benign	0.11	.;T;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.76	.;P;.
Vest4		0.45
MVP		0.10
MPC		0.57
ClinPred		0.010	T
GERP RS		3.7
PromoterAI		0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.31
gMVP		0.14
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs112277818; hg19: chr18-21083647;