Genetic Variant NM_014306.5:c.172+77A>G (chr22-32408678-T-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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

8 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 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.172+77A>G		intron	N/A	NP_055121.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RTCB	ENST00000216038.6	TSL:1 MANE Select	c.172+77A>G	intron	N/A	ENSP00000216038.5
RTCB	ENST00000923680.1		c.172+77A>G	intron	N/A	ENSP00000593739.1
RTCB	ENST00000953018.1		c.169+80A>G	intron	N/A	ENSP00000623077.1

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65527

AN:

151784

Hom.:

14590

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.536

AC:

11493

AN:

21430

American (AMR)

AF:

0.350

AC:

14728

AN:

42086

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

8494

AN:

22150

East Asian (EAS)

AF:

0.197

AC:

7122

AN:

36154

South Asian (SAS)

AF:

0.427

AC:

30842

AN:

72218

European-Finnish (FIN)

AF:

0.375

AC:

19594

AN:

52290

Middle Eastern (MID)

AF:

0.403

AC:

1852

AN:

4598

European-Non Finnish (NFE)

AF:

0.420

AC:

241460

AN:

574996

Other (OTH)

AF:

0.408

AC:

16611

AN:

40738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

10400

20799

31199

41598

51998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4960

9920

14880

19840

24800

<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:

0.432

AC:

65633

AN:

151902

Hom.:

14634

Cov.:

AF XY:

0.427

AC XY:

31693

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.532

AC:

22040

AN:

41438

American (AMR)

AF:

0.408

AC:

6206

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1350

AN:

3468

East Asian (EAS)

AF:

0.191

AC:

987

AN:

5176

South Asian (SAS)

AF:

0.415

AC:

2004

AN:

4824

European-Finnish (FIN)

AF:

0.357

AC:

3758

AN:

10530

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27908

AN:

67936

Other (OTH)

AF:

0.405

AC:

852

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1912

3824

5735

7647

9559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.417

Hom.:

22364

Bravo

AF:

0.439

Asia WGS

AF:

0.362

AC:

1261

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.4

(source)

DANN

Benign

0.73

PhyloP100

-0.11

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