rs2076043

Variant names:

• chr22-32408669-G-A
• rs2076043
• NM_014306.5:c.172+86C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.93).
• 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 rank	MANE	Protein	UniProt
RTCB	NM_014306.5	c.172+86C>T		intron_variant	Intron 2 of 11	ENST00000216038.6	NP_055121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTCB	ENST00000216038.6	c.172+86C>T		intron_variant	Intron 2 of 11	1	NM_014306.5	ENSP00000216038.5
RTCB	ENST00000463455.1	n.264+86C>T		intron_variant	Intron 2 of 2	2
RTCB	ENST00000487704.5	n.257+86C>T		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.867 AC: 17493 AN: 20174

American (AMR) AF: 0.661 AC: 26807 AN: 40574

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 14165 AN: 21578

East Asian (EAS) AF: 0.703 AC: 24760 AN: 35228

South Asian (SAS) AF: 0.727 AC: 50714 AN: 69802

European-Finnish (FIN) AF: 0.670 AC: 34475 AN: 51492

Middle Eastern (MID) AF: 0.702 AC: 3133 AN: 4464

European-Non Finnish (NFE) AF: 0.725 AC: 391587 AN: 539846

Other (OTH) AF: 0.718 AC: 28099 AN: 39150

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

African (AFR) AF: 0.866 AC: 35904 AN: 41452

American (AMR) AF: 0.704 AC: 10736 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2313 AN: 3466

East Asian (EAS) AF: 0.698 AC: 3609 AN: 5172

South Asian (SAS) AF: 0.717 AC: 3457 AN: 4820

European-Finnish (FIN) AF: 0.656 AC: 6899 AN: 10524

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48448 AN: 67914

Other (OTH) AF: 0.705 AC: 1488 AN: 2110

Alfa AF: 0.737 Hom.: 5436

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
PhyloP100		0.11
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: rs2076043; hg19: chr22-32804656;