9-4834394-A-G

Variant summary

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

The NM_005772.5(RCL1):c.584+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,056,858 control chromosomes in the GnomAD database, including 385,905 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 0.81 (50780 hom., cov: 29)
  • Exomes 𝑓: 0.86 (335125 hom.)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCL1	NM_005772.5	c.584+129A>G		intron_variant		ENST00000381750.9
RCL1	NM_001286699.2	c.110+129A>G		intron_variant
RCL1	NM_001286700.2	c.110+129A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9	c.584+129A>G		intron_variant		1	NM_005772.5	P1
RCL1	ENST00000442869.5	c.110+129A>G		intron_variant		3
RCL1	ENST00000473230.1	n.288+1166A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123260 AN: 151700 Hom.: 50757 Cov.: 29

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.859 AC: 777267 AN: 905042 Hom.: 335125 AF XY: 0.859 AC XY: 387755 AN XY: 451400

Gnomad4 AFR exome AF: 0.658

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.912

Gnomad4 NFE exome AF: 0.858

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.812 AC: 123332 AN: 151816 Hom.: 50780 Cov.: 29 AF XY: 0.819 AC XY: 60758 AN XY: 74168

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.844

Alfa AF: 0.844 Hom.: 73349

Bravo AF: 0.804

Asia WGS AF: 0.934 AC: 3248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.8
Dann	Benign	0.61

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: rs457287; hg19: chr9-4834394;