rs12530

Variant names:

• chr22-32387917-T-C
• rs12530
• NM_014306.5:c.*75A>G

Variant summary

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

The NM_014306.5(RTCB):​c.*75A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 979,458 control chromosomes in the GnomAD database, including 13,715 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1576 hom., cov: 33)
  • Exomes 𝑓: 0.16 (12139 hom.)
• Consequence: RTCB NM_014306.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 16 publications found

Genes affected

RTCB (HGNC:26935): (RNA 2',3'-cyclic phosphate and 5'-OH ligase) Enables RNA ligase (ATP) activity and vinculin binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Located in cytosol and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTCB	NM_014306.5	c.*75A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000216038.6	NP_055121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTCB	ENST00000216038.6	c.*75A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_014306.5	ENSP00000216038.5

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18935 AN: 152188 Hom.: 1575 Cov.: 33

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.159 AC: 131416 AN: 827152 Hom.: 12139 Cov.: 11 AF XY: 0.155 AC XY: 67378 AN XY: 433650

African (AFR) AF: 0.0301 AC: 642 AN: 21362

American (AMR) AF: 0.0737 AC: 3010 AN: 40846

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2724 AN: 21394

East Asian (EAS) AF: 0.000166 AC: 6 AN: 36238

South Asian (SAS) AF: 0.0629 AC: 4389 AN: 69776

European-Finnish (FIN) AF: 0.204 AC: 10384 AN: 50808

Middle Eastern (MID) AF: 0.136 AC: 522 AN: 3838

European-Non Finnish (NFE) AF: 0.192 AC: 104185 AN: 543562

Other (OTH) AF: 0.141 AC: 5554 AN: 39328

GnomAD4 genome AF: 0.124 AC: 18936 AN: 152306 Hom.: 1576 Cov.: 33 AF XY: 0.123 AC XY: 9160 AN XY: 74468

African (AFR) AF: 0.0335 AC: 1392 AN: 41592

American (AMR) AF: 0.0893 AC: 1367 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4830

European-Finnish (FIN) AF: 0.209 AC: 2213 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12721 AN: 68008

Other (OTH) AF: 0.110 AC: 232 AN: 2116

Alfa AF: 0.119 Hom.: 892

Bravo AF: 0.112

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.43
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs12530; hg19: chr22-32783904; COSMIC: COSV53281178; COSMIC: COSV53281178;