dbSNP rs5754073: RTCB:c.173-84C>T (chr22-32408326-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

7 publications found

Variant links:

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]

RTCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTCB	NM_014306.5	MANE Select	c.173-84C>T		intron	N/A	NP_055121.1	Q9Y3I0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RTCB	ENST00000216038.6	TSL:1 MANE Select	c.173-84C>T	intron	N/A	ENSP00000216038.5	Q9Y3I0
RTCB	ENST00000923680.1		c.173-84C>T	intron	N/A	ENSP00000593739.1
RTCB	ENST00000953018.1		c.170-84C>T	intron	N/A	ENSP00000623077.1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113833

AN:

151998

Hom.:

43049

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

9928

19857

29785

39714

49642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10616

21232

31848

42464

53080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.749

AC:

113947

AN:

152116

Hom.:

43098

Cov.:

AF XY:

0.746

AC XY:

55469

AN XY:

74348

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1432

2864

4296

5728

7160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.3

(source)

DANN

Benign

0.31

PhyloP100

0.070

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over