rs7860776

chr9-4836566-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005772.5(RCL1):c.584+2301G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,442 control chromosomes in the GnomAD database, including 5,539 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 0.26 (5539 hom., cov: 29)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCL1	NM_005772.5	c.584+2301G>A		intron_variant		ENST00000381750.9
RCL1	NM_001286699.2	c.110+2301G>A		intron_variant
RCL1	NM_001286700.2	c.110+2301G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9	c.584+2301G>A		intron_variant		1	NM_005772.5	P1
RCL1	ENST00000442869.5	c.110+2301G>A		intron_variant		3
RCL1	ENST00000473230.1	n.288+3338G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39185 AN: 151324 Hom.: 5541 Cov.: 29

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.259 AC: 39191 AN: 151442 Hom.: 5539 Cov.: 29 AF XY: 0.261 AC XY: 19295 AN XY: 73980

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.258

Alfa AF: 0.286 Hom.: 6612

Bravo AF: 0.255

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.14
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7860776; hg19: chr9-4836566;