rs5754073

Variant names:

• chr22-32408326-G-A
• rs5754073
• NM_014306.5:c.173-84C>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.173-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 1,148,618 control chromosomes in the GnomAD database, including 300,443 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 (43098 hom., cov: 31)
  • Exomes 𝑓: 0.72 (257345 hom.)
• Consequence: RTCB NM_014306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 7 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=-0.96).
• 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.173-84C>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.173-84C>T		intron_variant	Intron 2 of 11	1	NM_014306.5	ENSP00000216038.5
RTCB	ENST00000463455.1	n.265-84C>T		intron_variant	Intron 2 of 2	2
RTCB	ENST00000487704.5	n.258-84C>T		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113833 AN: 151998 Hom.: 43049 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.718 AC: 715341 AN: 996502 Hom.: 257345 AF XY: 0.717 AC XY: 364802 AN XY: 508848

African (AFR) AF: 0.869 AC: 20815 AN: 23946

American (AMR) AF: 0.665 AC: 24558 AN: 36948

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 14640 AN: 22280

East Asian (EAS) AF: 0.701 AC: 24711 AN: 35246

South Asian (SAS) AF: 0.727 AC: 51898 AN: 71416

European-Finnish (FIN) AF: 0.670 AC: 33493 AN: 49960

Middle Eastern (MID) AF: 0.702 AC: 3428 AN: 4884

European-Non Finnish (NFE) AF: 0.721 AC: 509879 AN: 707330

Other (OTH) AF: 0.717 AC: 31919 AN: 44492

GnomAD4 genome AF: 0.749 AC: 113947 AN: 152116 Hom.: 43098 Cov.: 31 AF XY: 0.746 AC XY: 55469 AN XY: 74348

African (AFR) AF: 0.866 AC: 35964 AN: 41524

American (AMR) AF: 0.704 AC: 10750 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3468

East Asian (EAS) AF: 0.697 AC: 3602 AN: 5166

South Asian (SAS) AF: 0.718 AC: 3449 AN: 4804

European-Finnish (FIN) AF: 0.656 AC: 6933 AN: 10564

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

European-Non Finnish (NFE) AF: 0.713 AC: 48512 AN: 67994

Other (OTH) AF: 0.706 AC: 1492 AN: 2114

Alfa AF: 0.730 Hom.: 11160

Bravo AF: 0.756

Asia WGS AF: 0.716 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.31
PhyloP100		0.070
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: rs5754073; hg19: chr22-32804313;