chr9-4819421-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005772.5(RCL1):​c.137-4127G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Consequence

RCL1
NM_005772.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

3 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RCL1NM_005772.5 linkc.137-4127G>T intron_variant Intron 1 of 8 ENST00000381750.9 NP_005763.3 Q9Y2P8-1
RCL1NM_001286699.2 linkc.-90-13733G>T intron_variant Intron 1 of 6 NP_001273628.1 Q9Y2P8Q5VZU3
RCL1NM_001286700.2 linkc.-162-4127G>T intron_variant Intron 1 of 7 NP_001273629.1 Q9Y2P8Q5VZU3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RCL1ENST00000381750.9 linkc.137-4127G>T intron_variant Intron 1 of 8 1 NM_005772.5 ENSP00000371169.4 Q9Y2P8-1
RCL1ENST00000442869.5 linkc.-162-4127G>T intron_variant Intron 1 of 7 3 ENSP00000412000.2 Q5VZU3
RCL1ENST00000381732.3 linkc.137-4127G>T intron_variant Intron 1 of 2 2 ENSP00000371151.3 Q5VYW8
RCL1ENST00000473230.1 linkn.142-4127G>T intron_variant Intron 1 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151974
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151974
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74226
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41360
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10548
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68000
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
57071

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
1.0
DANN
Benign
0.55
PhyloP100
-0.034

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

Other links and lift over

dbSNP: rs377186; hg19: chr9-4819421; API