rs2276314

Variant names:

• chr18-35977503-A-G
• rs2276314
• NM_031446.5:c.394A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-35977503-A-G
• chr18-35977503-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031446.5(RMP24):​c.394A>G​(p.Thr132Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,666 control chromosomes in the GnomAD database, including 41,320 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4804 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36516 hom.)
• Consequence: RMP24 NM_031446.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 30 publications found

Genes affected

RMP24 (HGNC:28802): (chromosome 18 open reading frame 21)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003577143).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMP24	NM_031446.5	c.394A>G	p.Thr132Ala	missense_variant	Exon 4 of 5	ENST00000592875.6	NP_113634.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C18orf21	ENST00000592875.6	c.394A>G	p.Thr132Ala	missense_variant	Exon 4 of 5	1	NM_031446.5	ENSP00000465517.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37513 AN: 151964 Hom.: 4802 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.241

GnomAD2 exomes AF: 0.229 AC: 57532 AN: 251336 AF XY: 0.230

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.221 AC: 322907 AN: 1461584 Hom.: 36516 Cov.: 33 AF XY: 0.223 AC XY: 161895 AN XY: 727096

African (AFR) AF: 0.319 AC: 10685 AN: 33472

American (AMR) AF: 0.176 AC: 7878 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7489 AN: 26122

East Asian (EAS) AF: 0.272 AC: 10792 AN: 39696

South Asian (SAS) AF: 0.241 AC: 20762 AN: 86206

European-Finnish (FIN) AF: 0.226 AC: 12059 AN: 53396

Middle Eastern (MID) AF: 0.274 AC: 1577 AN: 5766

European-Non Finnish (NFE) AF: 0.214 AC: 238049 AN: 1111840

Other (OTH) AF: 0.225 AC: 13616 AN: 60384

GnomAD4 genome AF: 0.247 AC: 37552 AN: 152082 Hom.: 4804 Cov.: 32 AF XY: 0.245 AC XY: 18252 AN XY: 74360

African (AFR) AF: 0.315 AC: 13061 AN: 41442

American (AMR) AF: 0.187 AC: 2855 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1302 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1122 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2297 AN: 10594

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15142 AN: 67998

Other (OTH) AF: 0.241 AC: 508 AN: 2108

Alfa AF: 0.229 Hom.: 16543

Bravo AF: 0.250

TwinsUK AF: 0.211 AC: 784

ALSPAC AF: 0.221 AC: 850

ESP6500AA AF: 0.315 AC: 1390

ESP6500EA AF: 0.223 AC: 1917

ExAC AF: 0.235 AC: 28481

Asia WGS AF: 0.210 AC: 728 AN: 3478

EpiCase AF: 0.220

EpiControl AF: 0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.013
DANN	Benign	0.29
DEOGEN2	Benign	0.0092	T;.;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.30	T;T;T;T;.
MetaRNN	Benign	0.0036	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L;.;.;.;.
PhyloP100		-1.0
PROVEAN	Benign	-1.3	.;.;N;.;.
REVEL	Benign	0.090
Sift	Benign	0.75	.;.;T;.;.
Sift4G	Benign	0.94	T;T;T;T;T
Polyphen		0.0040	B;.;.;.;.
Vest4		0.016
MPC		0.13
ClinPred		0.0068	T
GERP RS		-9.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.21
Mutation Taster		=97/3	polymorphism (auto)

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: rs2276314; hg19: chr18-33557466; COSMIC: COSV52449494; COSMIC: COSV52449494;