rs464921

Positions:

• chr6-33272729-A-G

Variant summary

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

The NM_022551.3(RPS18):​c.102+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,437,904 control chromosomes in the GnomAD database, including 15,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1277 hom., cov: 33)
  • Exomes 𝑓: 0.14 (13990 hom.)
• Consequence: RPS18 NM_022551.3 splice_region, intron
• Scores: Splicing: ADA: 0.001239
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

Genes affected

RPS18 (HGNC:10401): (ribosomal protein S18) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S13P family of ribosomal proteins. It is located in the cytoplasm. The gene product of the E. coli ortholog (ribosomal protein S13) is involved in the binding of fMet-tRNA, and thus, in the initiation of translation. This gene is an ortholog of mouse Ke3. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS18	NM_022551.3	c.102+3A>G		splice_region_variant, intron_variant		ENST00000439602.7	NP_072045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS18	ENST00000439602.7	c.102+3A>G		splice_region_variant, intron_variant		1	NM_022551.3	ENSP00000393241.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18162 AN: 152110 Hom.: 1274 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.159

GnomAD3 exomes AF: 0.137 AC: 34572 AN: 251472 Hom.: 2768 AF XY: 0.145 AC XY: 19696 AN XY: 135914

Gnomad AFR exome AF: 0.0563

Gnomad AMR exome AF: 0.0918

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.0703

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.0850

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.141 AC: 181528 AN: 1285676 Hom.: 13990 Cov.: 20 AF XY: 0.144 AC XY: 93642 AN XY: 648366

Gnomad4 AFR exome AF: 0.0510

Gnomad4 AMR exome AF: 0.0969

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.0650

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.0890

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.119 AC: 18176 AN: 152228 Hom.: 1277 Cov.: 33 AF XY: 0.118 AC XY: 8791 AN XY: 74436

Gnomad4 AFR AF: 0.0584

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.0809

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.162

Alfa AF: 0.150 Hom.: 1572

Bravo AF: 0.119

Asia WGS AF: 0.175 AC: 609 AN: 3478

EpiCase AF: 0.160

EpiControl AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.020		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: rs464921; hg19: chr6-33240506; COSMIC: COSV71403677; COSMIC: COSV71403677;