9-4877246-G-C

Variant names:

• chr9-4877246-G-C
• rs913258
• ENST00000445485.1:n.449-7242G>C

Variant summary

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

The ENST00000445485.1(RCL1):​n.449-7242G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,616 control chromosomes in the GnomAD database, including 15,961 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 0.36 (15961 hom., cov: 30)
• Consequence: RCL1 ENST00000445485.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	ENST00000445485.1	TSL:2	n.449-7242G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55186 AN: 151498 Hom.: 15905 Cov.: 30

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.365 AC: 55318 AN: 151616 Hom.: 15961 Cov.: 30 AF XY: 0.367 AC XY: 27209 AN XY: 74054

African (AFR) AF: 0.774 AC: 31971 AN: 41298

American (AMR) AF: 0.299 AC: 4559 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3464

East Asian (EAS) AF: 0.745 AC: 3830 AN: 5140

South Asian (SAS) AF: 0.336 AC: 1606 AN: 4776

European-Finnish (FIN) AF: 0.186 AC: 1948 AN: 10494

Middle Eastern (MID) AF: 0.191 AC: 55 AN: 288

European-Non Finnish (NFE) AF: 0.148 AC: 10052 AN: 67898

Other (OTH) AF: 0.308 AC: 649 AN: 2106

Alfa AF: 0.258 Hom.: 1183

Bravo AF: 0.391

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.19

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs913258;

hg19: chr9-4877246;