9-4877246-G-C

Position:

• chr9-4877246-G-C

Variant summary

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

The ENST00000445485.1(RCL1):​n.449-7242G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,616 control chromosomes in the GnomAD database, including 15,961 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 0.36 (15961 hom., cov: 30)
• Consequence: RCL1 ENST00000445485.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000445485.1	n.449-7242G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55186 AN: 151498 Hom.: 15905 Cov.: 30

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.365 AC: 55318 AN: 151616 Hom.: 15961 Cov.: 30 AF XY: 0.367 AC XY: 27209 AN XY: 74054

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.308

Alfa AF: 0.258 Hom.: 1183

Bravo AF: 0.391

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs913258; hg19: chr9-4877246;