9-4856877-G-A

Position:

• chr9-4856877-G-A

Variant summary

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

The NM_005772.5(RCL1):​c.972-3248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,144 control chromosomes in the GnomAD database, including 2,763 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 0.16 (2763 hom., cov: 32)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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]

LOC124902113 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCL1	NM_005772.5	c.972-3248G>A		intron_variant		ENST00000381750.9	NP_005763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.972-3248G>A		intron_variant		1	NM_005772.5	ENSP00000371169.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24486 AN: 152026 Hom.: 2758 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.161 AC: 24491 AN: 152144 Hom.: 2763 Cov.: 32 AF XY: 0.163 AC XY: 12125 AN XY: 74390

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.154

Alfa AF: 0.196 Hom.: 4106

Bravo AF: 0.153

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.69

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: rs10758658; hg19: chr9-4856877; COSMIC: COSV67754425; COSMIC: COSV67754425;