dbSNP rs1053872: RCL1:c.*368G>C (chr9-4860643-G-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_005772.5(RCL1):c.*368G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 186,736 control chromosomes in the GnomAD database, including 9,222 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 0.30 ( 8346 hom., cov: 33)

Exomes 𝑓: 0.20 ( 876 hom. )

Consequence

RCL1
NM_005772.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

13 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005772.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RCL1	NM_005772.5	MANE Select	c.*368G>C	3_prime_UTR	Exon 9 of 9	NP_005763.3
RCL1	NM_001286699.2		c.*368G>C	3_prime_UTR	Exon 7 of 7	NP_001273628.1
RCL1	NM_001286700.2		c.*368G>C	3_prime_UTR	Exon 8 of 8	NP_001273629.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RCL1	ENST00000381750.9	TSL:1 MANE Select	c.*368G>C	3_prime_UTR	Exon 9 of 9	ENSP00000371169.4
RCL1	ENST00000448872.6	TSL:1	c.*368G>C	3_prime_UTR	Exon 5 of 5	ENSP00000388096.2
RCL1	ENST00000445485.1	TSL:2	n.190G>C	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45451

AN:

151938

Hom.:

8324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.200

AC:

6952

AN:

34680

Hom.:

876

Cov.:

AF XY:

0.197

AC XY:

3477

AN XY:

17686

show subpopulations

African (AFR)

AF:

0.460

AC:

296

AN:

644

American (AMR)

AF:

0.233

AC:

147

AN:

632

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

190

AN:

1066

East Asian (EAS)

AF:

0.490

AC:

537

AN:

1096

South Asian (SAS)

AF:

0.155

AC:

485

AN:

3136

European-Finnish (FIN)

AF:

0.215

AC:

368

AN:

1714

Middle Eastern (MID)

AF:

0.126

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.185

AC:

4402

AN:

23776

Other (OTH)

AF:

0.208

AC:

502

AN:

2418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

271

542

813

1084

1355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.299

AC:

45516

AN:

152056

Hom.:

8346

Cov.:

AF XY:

0.296

AC XY:

22014

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.505

AC:

20908

AN:

41440

American (AMR)

AF:

0.239

AC:

3651

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

676

AN:

3470

East Asian (EAS)

AF:

0.526

AC:

2710

AN:

5152

South Asian (SAS)

AF:

0.200

AC:

967

AN:

4824

European-Finnish (FIN)

AF:

0.223

AC:

2361

AN:

10584

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13507

AN:

67994

Other (OTH)

AF:

0.255

AC:

539

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1501

3002

4502

6003

7504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.119

Hom.:

183

Bravo

AF:

0.312

Asia WGS

AF:

0.353

AC:

1226

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.3

(source)

DANN

Benign

0.53

PhyloP100

0.52

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