NM_005772.5:c.971+591T>C

Variant summary

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

The NM_005772.5(RCL1):​c.971+591T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,082 control chromosomes in the GnomAD database, including 8,582 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 0.33 ( 8582 hom., cov: 32)

Consequence

RCL1
NM_005772.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.685

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]
MIR101-2 (HGNC:31489): (microRNA 101-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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=-0.88).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RCL1NM_005772.5 linkc.971+591T>C intron_variant Intron 8 of 8 ENST00000381750.9 NP_005763.3 Q9Y2P8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RCL1ENST00000381750.9 linkc.971+591T>C intron_variant Intron 8 of 8 1 NM_005772.5 ENSP00000371169.4 Q9Y2P8-1

Frequencies

GnomAD3 genomes
AF:
0.330
AC:
50192
AN:
151964
Hom.:
8571
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.377
Gnomad AMI
AF:
0.291
Gnomad AMR
AF:
0.358
Gnomad ASJ
AF:
0.196
Gnomad EAS
AF:
0.251
Gnomad SAS
AF:
0.456
Gnomad FIN
AF:
0.372
Gnomad MID
AF:
0.203
Gnomad NFE
AF:
0.295
Gnomad OTH
AF:
0.304
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.330
AC:
50246
AN:
152082
Hom.:
8582
Cov.:
32
AF XY:
0.336
AC XY:
24974
AN XY:
74350
show subpopulations
African (AFR)
AF:
0.377
AC:
15615
AN:
41454
American (AMR)
AF:
0.358
AC:
5476
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.196
AC:
679
AN:
3468
East Asian (EAS)
AF:
0.251
AC:
1301
AN:
5180
South Asian (SAS)
AF:
0.456
AC:
2202
AN:
4828
European-Finnish (FIN)
AF:
0.372
AC:
3924
AN:
10554
Middle Eastern (MID)
AF:
0.207
AC:
61
AN:
294
European-Non Finnish (NFE)
AF:
0.295
AC:
20072
AN:
67996
Other (OTH)
AF:
0.309
AC:
651
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1734
3468
5203
6937
8671
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
504
1008
1512
2016
2520
<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:
0.314
Hom.:
1607
Bravo
AF:
0.328
Asia WGS
AF:
0.400
AC:
1391
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.2
DANN
Benign
0.30
PhyloP100
-0.69
Mutation Taster
=100/0
polymorphism (auto)

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: rs12375841; hg19: chr9-4850141; COSMIC: COSV63004602; COSMIC: COSV63004602; API