rs462480

Variant names:

• chr9-4850436-G-A
• rs462480
• NM_005772.5:c.971+886G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-4850436-G-A
• chr9-4850436-G-C
• chr9-4850436-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005772.5(RCL1):​c.971+886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 225,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 26)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 10 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:):

MIR101-2 (HGNC:31489): (microRNA 101-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.971+886G>A		intron_variant	Intron 8 of 8	ENST00000381750.9	NP_005763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.971+886G>A		intron_variant	Intron 8 of 8	1	NM_005772.5	ENSP00000371169.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000888 AC: 2 AN: 225220 Hom.: 0 AF XY: 0.0000158 AC XY: 2 AN XY: 126900

African (AFR) AF: 0.000245 AC: 2 AN: 8168

American (AMR) AF: 0.00 AC: 0 AN: 30930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8248

East Asian (EAS) AF: 0.00 AC: 0 AN: 10362

South Asian (SAS) AF: 0.00 AC: 0 AN: 37038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 95252

Other (OTH) AF: 0.00 AC: 0 AN: 8752

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 3287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.14
DANN	Benign	0.93
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs462480; hg19: chr9-4850436;