Genetic Variant RCL1:c.584+129A>G (chr9-4834394-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005772.5(RCL1):c.584+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,056,858 control chromosomes in the GnomAD database, including 385,905 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 0.81 ( 50780 hom., cov: 29)

Exomes 𝑓: 0.86 ( 335125 hom. )

Consequence

RCL1
NM_005772.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

Publications

11 publications found

Variant links:

Genes affected

RCL1 (HGNC:17687): (RNA terminal phosphate cyclase like 1) Predicted to enable endoribonuclease activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

RCL1 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RCL1	NM_005772.5 link	c.584+129A>G	intron_variant	Intron 5 of 8	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2 link	c.110+129A>G	intron_variant	Intron 3 of 6		NP_001273628.1
RCL1	NM_001286700.2 link	c.110+129A>G	intron_variant	Intron 4 of 7		NP_001273629.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
RCL1	ENST00000381750.9 link	c.584+129A>G	intron_variant	Intron 5 of 8	1	NM_005772.5	ENSP00000371169.4
RCL1	ENST00000442869.5 link	c.110+129A>G	intron_variant	Intron 4 of 7	3		ENSP00000412000.2
RCL1	ENST00000473230.1 link	n.288+1166A>G	intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.813

AC:

123260

AN:

151700

Hom.:

50757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.773

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.865

Gnomad FIN

AF:

0.919

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.854

Gnomad OTH

AF:

0.842

GnomAD4 exome

AF:

0.859

AC:

777267

AN:

905042

Hom.:

335125

AF XY:

0.859

AC XY:

387755

AN XY:

451400

show subpopulations

African (AFR)

AF:

0.658

AC:

13043

AN:

19834

American (AMR)

AF:

0.915

AC:

19147

AN:

20928

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

12017

AN:

15298

East Asian (EAS)

AF:

0.999

AC:

27127

AN:

27146

South Asian (SAS)

AF:

0.857

AC:

47817

AN:

55822

European-Finnish (FIN)

AF:

0.912

AC:

23715

AN:

26008

Middle Eastern (MID)

AF:

0.785

AC:

2078

AN:

2646

European-Non Finnish (NFE)

AF:

0.858

AC:

599729

AN:

699006

Other (OTH)

AF:

0.850

AC:

32594

AN:

38354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

5095

10190

15285

20380

25475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13032

26064

39096

52128

65160

<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:

0.812

AC:

123332

AN:

151816

Hom.:

50780

Cov.:

AF XY:

0.819

AC XY:

60758

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.666

AC:

27517

AN:

41316

American (AMR)

AF:

0.873

AC:

13320

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.773

AC:

2683

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5171

AN:

5180

South Asian (SAS)

AF:

0.867

AC:

4170

AN:

4812

European-Finnish (FIN)

AF:

0.919

AC:

9642

AN:

10496

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.854

AC:

58050

AN:

67968

Other (OTH)

AF:

0.844

AC:

1785

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1091

2182

3273

4364

5455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.830

Hom.:

111648

Bravo

AF:

0.804

Asia WGS

AF:

0.934

AC:

3248

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.61

PhyloP100

-0.018

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over