rs2072818

Positions:

• chr22-32395016-A-C
• chr22-32395016-A-T

Variant summary

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

The NM_014306.5(RTCB):​c.1179+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,600,144 control chromosomes in the GnomAD database, including 248,165 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 0.62 (30664 hom., cov: 33)
  • Exomes 𝑓: 0.54 (217501 hom.)
• Consequence: RTCB NM_014306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTCB	NM_014306.5	c.1179+10T>G		intron_variant		ENST00000216038.6	NP_055121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTCB	ENST00000216038.6	c.1179+10T>G		intron_variant		1	NM_014306.5	ENSP00000216038.5

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94293 AN: 152034 Hom.: 30628 Cov.: 33

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.573

GnomAD3 exomes AF: 0.555 AC: 137917 AN: 248518 Hom.: 39489 AF XY: 0.547 AC XY: 73440 AN XY: 134274

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.577

Gnomad SAS exome AF: 0.529

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.531

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.544 AC: 788354 AN: 1447992 Hom.: 217501 Cov.: 31 AF XY: 0.541 AC XY: 388939 AN XY: 718262

Gnomad4 AFR exome AF: 0.859

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.620 AC: 94392 AN: 152152 Hom.: 30664 Cov.: 33 AF XY: 0.616 AC XY: 45856 AN XY: 74388

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.576

Alfa AF: 0.542 Hom.: 5698

Bravo AF: 0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
DANN	Benign	0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2072818; hg19: chr22-32791003;