rs2276314

chr18-35977503-A-Gchr18-35977503-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031446.5(C18orf21):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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (4804 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36516 hom.)
• Consequence: C18orf21 NM_031446.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

C18orf21 (HGNC:28802): (chromosome 18 open reading frame 21)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
C18orf21	NM_031446.5	c.394A>G	p.Thr132Ala	missense_variant	4/5	ENST00000592875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C18orf21	ENST00000592875.6	c.394A>G	p.Thr132Ala	missense_variant	4/5	1	NM_031446.5	P1

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

GnomAD3 exomes AF: 0.229 AC: 57532 AN: 251336 Hom.: 6958 AF XY: 0.230 AC XY: 31285 AN XY: 135828

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 SAS exome AF: 0.238

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

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.225

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

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.241

Alfa AF: 0.223 Hom.: 7768

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;.;.;.;.
MutationTaster	Benign	1.0	P;P
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

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

Other links and lift over

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