9-4814948-G-C

Variant names:

• chr9-4814948-G-C
• rs13300663
• NM_005772.5:c.137-8600G>C

Variant summary

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

The NM_005772.5(RCL1):​c.137-8600G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,528 control chromosomes in the GnomAD database, including 3,395 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 0.19 (3395 hom., cov: 32)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.137-8600G>C		intron_variant	Intron 1 of 8	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2	c.-90-18206G>C		intron_variant	Intron 1 of 6		NP_001273628.1
RCL1	NM_001286700.2	c.-162-8600G>C		intron_variant	Intron 1 of 7		NP_001273629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.137-8600G>C		intron_variant	Intron 1 of 8	1	NM_005772.5	ENSP00000371169.4
RCL1	ENST00000442869.5	c.-162-8600G>C		intron_variant	Intron 1 of 7	3		ENSP00000412000.2
RCL1	ENST00000381732.3	c.137-8600G>C		intron_variant	Intron 1 of 2	2		ENSP00000371151.3
RCL1	ENST00000473230.1	n.142-8600G>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28196 AN: 151410 Hom.: 3399 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.186 AC: 28197 AN: 151528 Hom.: 3395 Cov.: 32 AF XY: 0.187 AC XY: 13812 AN XY: 74034

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.177

Alfa AF: 0.103 Hom.: 164

Bravo AF: 0.177

Asia WGS AF: 0.363 AC: 1260 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.40

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: rs13300663; hg19: chr9-4814948;