9-4856877-G-A

Variant names:

• chr9-4856877-G-A
• rs10758658
• NM_005772.5:c.972-3248G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 35 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]

LOC124902113 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005772.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	NM_005772.5	MANE Select	c.972-3248G>A		intron	N/A	NP_005763.3
	RCL1	NM_001286699.2		c.498-3248G>A		intron	N/A	NP_001273628.1
	RCL1	NM_001286700.2		c.498-3248G>A		intron	N/A	NP_001273629.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	ENST00000381750.9	TSL:1 MANE Select	c.972-3248G>A		intron	N/A	ENSP00000371169.4
	RCL1	ENST00000448872.6	TSL:1	c.414-3248G>A		intron	N/A	ENSP00000388096.2
	RCL1	ENST00000442869.5	TSL:3	c.498-3248G>A		intron	N/A	ENSP00000412000.2

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

African (AFR) AF: 0.0403 AC: 1672 AN: 41512

American (AMR) AF: 0.170 AC: 2598 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3472

East Asian (EAS) AF: 0.539 AC: 2780 AN: 5156

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4824

European-Finnish (FIN) AF: 0.221 AC: 2344 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12886 AN: 67984

Other (OTH) AF: 0.154 AC: 323 AN: 2104

Alfa AF: 0.188 Hom.: 9853

Bravo AF: 0.153

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.69
PhyloP100		-1.8
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: rs10758658; hg19: chr9-4856877; COSMIC: COSV67754425; COSMIC: COSV67754425;