rs2076044

Positions:

• chr22-32408678-T-C

Variant summary

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

The NM_014306.5(RTCB):​c.172+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,018,562 control chromosomes in the GnomAD database, including 88,154 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 0.43 (14634 hom., cov: 32)
  • Exomes 𝑓: 0.41 (73520 hom.)
• Consequence: RTCB NM_014306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTCB	NM_014306.5	c.172+77A>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.172+77A>G		intron_variant		1	NM_014306.5	ENSP00000216038	P1
RTCB	ENST00000463455.1	n.264+77A>G		intron_variant, non_coding_transcript_variant		2
RTCB	ENST00000487704.5	n.257+77A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65527 AN: 151784 Hom.: 14590 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.406 AC: 352196 AN: 866660 Hom.: 73520 AF XY: 0.407 AC XY: 184793 AN XY: 454184

Gnomad4 AFR exome AF: 0.536

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.432 AC: 65633 AN: 151902 Hom.: 14634 Cov.: 32 AF XY: 0.427 AC XY: 31693 AN XY: 74250

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.405

Alfa AF: 0.413 Hom.: 17344

Bravo AF: 0.439

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.73

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: rs2076044; hg19: chr22-32804665;