rs5994562

Variant names:

• chr22-32392089-T-A
• rs5994562
• NM_014306.5:c.1410+151A>T

Your query was ambiguous. Multiple possible variants found:

• chr22-32392089-T-A
• chr22-32392089-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014306.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTCB	NM_014306.5	MANE Select	c.1410+151A>T		intron	N/A	NP_055121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTCB	ENST00000216038.6	TSL:1 MANE Select	c.1410+151A>T		intron	N/A	ENSP00000216038.5

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

African (AFR) AF: 0.851 AC: 11709 AN: 13766

American (AMR) AF: 0.556 AC: 9453 AN: 17016

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 6152 AN: 13928

East Asian (EAS) AF: 0.540 AC: 17145 AN: 31778

South Asian (SAS) AF: 0.518 AC: 19492 AN: 37654

European-Finnish (FIN) AF: 0.522 AC: 17016 AN: 32622

Middle Eastern (MID) AF: 0.565 AC: 1186 AN: 2098

European-Non Finnish (NFE) AF: 0.535 AC: 192537 AN: 359692

Other (OTH) AF: 0.547 AC: 15600 AN: 28502

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

African (AFR) AF: 0.843 AC: 34994 AN: 41490

American (AMR) AF: 0.574 AC: 8745 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3464

East Asian (EAS) AF: 0.558 AC: 2878 AN: 5156

South Asian (SAS) AF: 0.521 AC: 2510 AN: 4816

European-Finnish (FIN) AF: 0.513 AC: 5399 AN: 10522

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 36284 AN: 67920

Other (OTH) AF: 0.575 AC: 1213 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.52
DANN	Benign	0.18
PhyloP100		-1.7
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: rs5994562; hg19: chr22-32788076; COSMIC: COSV53279272;