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:

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=-0.91).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5 link	c.*368G>C	3_prime_UTR_variant	Exon 9 of 9	ENST00000381750.9	NP_005763.3	Q9Y2P8-1
RCL1	NM_001286699.2 link	c.*368G>C	3_prime_UTR_variant	Exon 7 of 7		NP_001273628.1	Q9Y2P8Q5VZU3
RCL1	NM_001286700.2 link	c.*368G>C	3_prime_UTR_variant	Exon 8 of 8		NP_001273629.1	Q9Y2P8Q5VZU3
RCL1	NM_001286701.2 link	c.*368G>C	3_prime_UTR_variant	Exon 5 of 5		NP_001273630.1	Q9Y2P8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9 link	c.*368G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_005772.5	ENSP00000371169.4		Q9Y2P8-1

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

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

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 v4.3

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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rs1053872

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