rs377186

Positions:

• chr9-4819421-G-A
• chr9-4819421-G-C
• chr9-4819421-G-T

Variant summary

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

The NM_005772.5(RCL1):​c.137-4127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,022 control chromosomes in the GnomAD database, including 12,314 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 0.39 (12314 hom., cov: 33)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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 = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCL1	NM_005772.5	c.137-4127G>A		intron_variant		ENST00000381750.9
RCL1	NM_001286699.2	c.-90-13733G>A		intron_variant
RCL1	NM_001286700.2	c.-162-4127G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9	c.137-4127G>A		intron_variant		1	NM_005772.5	P1
RCL1	ENST00000381732.3	c.137-4127G>A		intron_variant		2
RCL1	ENST00000442869.5	c.-162-4127G>A		intron_variant		3
RCL1	ENST00000473230.1	n.142-4127G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58838 AN: 151904 Hom.: 12316 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.387 AC: 58851 AN: 152022 Hom.: 12314 Cov.: 33 AF XY: 0.393 AC XY: 29178 AN XY: 74308

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.395

Alfa AF: 0.445 Hom.: 26467

Bravo AF: 0.378

Asia WGS AF: 0.397 AC: 1380 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	1.3
DANN	Benign	0.62

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: rs377186; hg19: chr9-4819421;