22-32392089-T-A

Position:

• chr22-32392089-T-A

Variant summary

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

The NM_014306.5(RTCB):​c.1410+151A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 688,980 control chromosomes in the GnomAD database, including 110,854 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 (30653 hom., cov: 32)
  • Exomes 𝑓: 0.54 (80201 hom.)
• Consequence: RTCB NM_014306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTCB	NM_014306.5	c.1410+151A>T		intron_variant		ENST00000216038.6	NP_055121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTCB	ENST00000216038.6	c.1410+151A>T		intron_variant		1	NM_014306.5	ENSP00000216038	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94240 AN: 151806 Hom.: 30615 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.541 AC: 290290 AN: 537056 Hom.: 80201 AF XY: 0.536 AC XY: 148550 AN XY: 277016

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome AF: 0.621 AC: 94341 AN: 151924 Hom.: 30653 Cov.: 32 AF XY: 0.617 AC XY: 45818 AN XY: 74236

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.575

Alfa AF: 0.583 Hom.: 3367

Bravo AF: 0.634

Asia WGS AF: 0.566 AC: 1968 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.52
DANN	Benign	0.18

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: rs5994562; hg19: chr22-32788076; COSMIC: COSV53279272;