rs2236496

chr9-4844265-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCL1	NM_005772.5	c.711-260T>C		intron_variant		ENST00000381750.9
RCL1	NM_001286699.2	c.237-260T>C		intron_variant
RCL1	NM_001286700.2	c.237-260T>C		intron_variant
RCL1	NM_001286701.2	c.153-260T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9	c.711-260T>C		intron_variant		1	NM_005772.5	P1

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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.176

Alfa AF: 0.190 Hom.: 1349

Bravo AF: 0.188

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.43
Dann	Benign	0.45

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

LitVar

Other links and lift over

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