rs7860776

Variant names:

• chr9-4836566-G-A
• rs7860776
• NM_005772.5:c.584+2301G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-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 rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.584+2301G>A		intron_variant	Intron 5 of 8	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2	c.110+2301G>A		intron_variant	Intron 3 of 6		NP_001273628.1
RCL1	NM_001286700.2	c.110+2301G>A		intron_variant	Intron 4 of 7		NP_001273629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.584+2301G>A		intron_variant	Intron 5 of 8	1	NM_005772.5	ENSP00000371169.4
RCL1	ENST00000442869.5	c.110+2301G>A		intron_variant	Intron 4 of 7	3		ENSP00000412000.2
RCL1	ENST00000473230.1	n.288+3338G>A		intron_variant	Intron 3 of 3	3
RCL1	ENST00000381730.5	c.-200G>A		upstream_gene_variant		3		ENSP00000371149.1

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

African (AFR) AF: 0.165 AC: 6796 AN: 41244

American (AMR) AF: 0.314 AC: 4784 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 966 AN: 3450

East Asian (EAS) AF: 0.136 AC: 696 AN: 5126

South Asian (SAS) AF: 0.390 AC: 1862 AN: 4778

European-Finnish (FIN) AF: 0.318 AC: 3325 AN: 10472

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19888 AN: 67832

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.283 Hom.: 8360

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
PhyloP100		-1.1
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7860776; hg19: chr9-4836566;