ENST00000445485.1:n.449-8184T>C

Variant names:

• chr9-4876304-T-C
• rs7869592
• ENST00000445485.1:n.449-8184T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000445485.1(RCL1):​n.449-8184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,932 control chromosomes in the GnomAD database, including 17,696 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 0.48 (17696 hom., cov: 32)
• Consequence: RCL1 ENST00000445485.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445485.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	ENST00000445485.1	TSL:2	n.449-8184T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72788 AN: 151814 Hom.: 17681 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.512

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.479 AC: 72827 AN: 151932 Hom.: 17696 Cov.: 32 AF XY: 0.477 AC XY: 35432 AN XY: 74228

African (AFR) AF: 0.502 AC: 20783 AN: 41416

American (AMR) AF: 0.426 AC: 6516 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1806 AN: 5174

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4810

European-Finnish (FIN) AF: 0.496 AC: 5228 AN: 10548

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33567 AN: 67920

Other (OTH) AF: 0.513 AC: 1086 AN: 2116

Alfa AF: 0.483 Hom.: 9455

Bravo AF: 0.481

Asia WGS AF: 0.373 AC: 1302 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7869592; hg19: chr9-4876304;