rs2076043

Positions:

• chr22-32408669-G-A

Variant summary

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

The NM_014306.5(RTCB):​c.172+86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 974,224 control chromosomes in the GnomAD database, including 256,284 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 0.75 (43010 hom., cov: 32)
  • Exomes 𝑓: 0.72 (213274 hom.)
• Consequence: RTCB NM_014306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTCB	NM_014306.5	c.172+86C>T		intron_variant		ENST00000216038.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTCB	ENST00000216038.6	c.172+86C>T		intron_variant		1	NM_014306.5	P1
RTCB	ENST00000463455.1	n.264+86C>T		intron_variant, non_coding_transcript_variant		2
RTCB	ENST00000487704.5	n.257+86C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113665 AN: 151798 Hom.: 42961 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.719 AC: 591233 AN: 822308 Hom.: 213274 AF XY: 0.717 AC XY: 310140 AN XY: 432360

Gnomad4 AFR exome AF: 0.867

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.670

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.718

GnomAD4 genome AF: 0.749 AC: 113779 AN: 151916 Hom.: 43010 Cov.: 32 AF XY: 0.746 AC XY: 55389 AN XY: 74244

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.705

Alfa AF: 0.732 Hom.: 5140

Bravo AF: 0.757

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.41

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: rs2076043; hg19: chr22-32804656;