dbSNP rs2072818: RTCB:c.1179+10T>G (chr22-32395016-A-C) – 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.1179+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,600,144 control chromosomes in the GnomAD database, including 248,165 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 ( 30664 hom., cov: 33)

Exomes 𝑓: 0.54 ( 217501 hom. )

Consequence

RTCB
NM_014306.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

10 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

new If you want to explore the variant's impact on the transcript NM_014306.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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.1179+10T>G		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.1179+10T>G	intron	N/A	ENSP00000216038.5	Q9Y3I0
RTCB	ENST00000923680.1		c.1197+10T>G	intron	N/A	ENSP00000593739.1
RTCB	ENST00000953018.1		c.1194+10T>G	intron	N/A	ENSP00000623077.1

Frequencies

GnomAD3 genomes

AF:

0.620

AC:

94293

AN:

152034

Hom.:

30628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.843

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.574

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.573

GnomAD2 exomes

AF:

0.555

AC:

137917

AN:

248518

AF XY:

0.547

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.531

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.544

AC:

788354

AN:

1447992

Hom.:

217501

Cov.:

AF XY:

0.541

AC XY:

388939

AN XY:

718262

show subpopulations

African (AFR)

AF:

0.859

AC:

28529

AN:

33228

American (AMR)

AF:

0.563

AC:

24807

AN:

44084

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

11416

AN:

25890

East Asian (EAS)

AF:

0.547

AC:

21538

AN:

39380

South Asian (SAS)

AF:

0.529

AC:

45077

AN:

85210

European-Finnish (FIN)

AF:

0.520

AC:

27730

AN:

53294

Middle Eastern (MID)

AF:

0.570

AC:

3239

AN:

5678

European-Non Finnish (NFE)

AF:

0.539

AC:

593256

AN:

1101430

Other (OTH)

AF:

0.548

AC:

32762

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16268

32536

48805

65073

81341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17060

34120

51180

68240

85300

<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:

0.620

AC:

94392

AN:

152152

Hom.:

30664

Cov.:

AF XY:

0.616

AC XY:

45856

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.843

AC:

34996

AN:

41522

American (AMR)

AF:

0.574

AC:

8774

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1551

AN:

3470

East Asian (EAS)

AF:

0.557

AC:

2882

AN:

5170

South Asian (SAS)

AF:

0.520

AC:

2507

AN:

4824

European-Finnish (FIN)

AF:

0.511

AC:

5400

AN:

10570

Middle Eastern (MID)

AF:

0.555

AC:

162

AN:

292

European-Non Finnish (NFE)

AF:

0.534

AC:

36300

AN:

67998

Other (OTH)

AF:

0.576

AC:

1215

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1745

3490

5235

6980

8725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.557

Hom.:

13371

Bravo

AF:

0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.17

(source)

DANN

Benign

0.22

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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