9-4845520-A-G

Variant names:

• chr9-4845520-A-G
• rs10815094
• NM_005772.5:c.867+839A>G

Variant summary

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

The NM_005772.5(RCL1):​c.867+839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,214 control chromosomes in the GnomAD database, including 3,252 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 (3252 hom., cov: 33)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 10 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.867+839A>G		intron_variant	Intron 7 of 8	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2	c.393+839A>G		intron_variant	Intron 5 of 6		NP_001273628.1
RCL1	NM_001286700.2	c.393+839A>G		intron_variant	Intron 6 of 7		NP_001273629.1
RCL1	NM_001286701.2	c.309+839A>G		intron_variant	Intron 3 of 4		NP_001273630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.867+839A>G		intron_variant	Intron 7 of 8	1	NM_005772.5	ENSP00000371169.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28854 AN: 152096 Hom.: 3242 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.185

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: 0.176

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

GnomAD4 genome AF: 0.190 AC: 28885 AN: 152214 Hom.: 3252 Cov.: 33 AF XY: 0.190 AC XY: 14164 AN XY: 74420

African (AFR) AF: 0.121 AC: 5019 AN: 41550

American (AMR) AF: 0.186 AC: 2851 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2835 AN: 5178

South Asian (SAS) AF: 0.219 AC: 1055 AN: 4828

European-Finnish (FIN) AF: 0.223 AC: 2358 AN: 10578

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

European-Non Finnish (NFE) AF: 0.199 AC: 13521 AN: 67998

Other (OTH) AF: 0.175 AC: 371 AN: 2114

Alfa AF: 0.183 Hom.: 2657

Bravo AF: 0.186

Asia WGS AF: 0.339 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.5
DANN	Benign	0.87
PhyloP100		0.75
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: rs10815094; hg19: chr9-4845520; COSMIC: COSV63004697; COSMIC: COSV63004697;