rs2236496

Variant names:

• chr9-4844265-T-C
• rs2236496
• NM_005772.5:c.711-260T>C

Variant summary

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

The NM_005772.5(RCL1):​c.711-260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,106 control chromosomes in the GnomAD database, including 3,276 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 0.19 (3276 hom., cov: 32)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 26 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005772.5. 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
	RCL1	NM_005772.5	MANE Select	c.711-260T>C		intron	N/A	NP_005763.3
	RCL1	NM_001286699.2		c.237-260T>C		intron	N/A	NP_001273628.1	Q5VZU3
	RCL1	NM_001286700.2		c.237-260T>C		intron	N/A	NP_001273629.1	Q5VZU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	ENST00000381750.9	TSL:1 MANE Select	c.711-260T>C		intron	N/A	ENSP00000371169.4	Q9Y2P8-1
	RCL1	ENST00000448872.6	TSL:1	c.153-260T>C		intron	N/A	ENSP00000388096.2	Q9Y2P8-2
	RCL1	ENST00000442869.5	TSL:3	c.237-260T>C		intron	N/A	ENSP00000412000.2	Q5VZU3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29162 AN: 151988 Hom.: 3269 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.192 AC: 29190 AN: 152106 Hom.: 3276 Cov.: 32 AF XY: 0.192 AC XY: 14305 AN XY: 74342

African (AFR) AF: 0.128 AC: 5319 AN: 41506

American (AMR) AF: 0.187 AC: 2860 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 674 AN: 3462

East Asian (EAS) AF: 0.547 AC: 2823 AN: 5164

South Asian (SAS) AF: 0.219 AC: 1051 AN: 4810

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10560

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13537 AN: 68002

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.200 Hom.: 6742

Bravo AF: 0.188

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.45
PhyloP100		-3.0
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

Other links and lift over

dbSNP: rs2236496; hg19: chr9-4844265; COSMIC: COSV67754406; COSMIC: COSV67754406;