rs12375841

chr9-4850141-T-C

Variant summary

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

The NM_005772.5(RCL1):c.971+591T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,082 control chromosomes in the GnomAD database, including 8,582 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 0.33 (8582 hom., cov: 32)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCL1	NM_005772.5	c.971+591T>C		intron_variant		ENST00000381750.9
RCL1	NM_001286699.2	c.497+591T>C		intron_variant
RCL1	NM_001286700.2	c.497+591T>C		intron_variant
RCL1	NM_001286701.2	c.413+591T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9	c.971+591T>C		intron_variant		1	NM_005772.5	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50192 AN: 151964 Hom.: 8571 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.330 AC: 50246 AN: 152082 Hom.: 8582 Cov.: 32 AF XY: 0.336 AC XY: 24974 AN XY: 74350

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.309

Alfa AF: 0.313 Hom.: 1552

Bravo AF: 0.328

Asia WGS AF: 0.400 AC: 1391 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	2.2
Dann	Benign	0.30

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: rs12375841; hg19: chr9-4850141; COSMIC: COSV63004602; COSMIC: COSV63004602;