9-4850436-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005772.5(RCL1):​c.971+886G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 374,862 control chromosomes in the GnomAD database, including 59,729 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 0.57 (24638 hom., cov: 26)
  • Exomes 𝑓: 0.56 (35091 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 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.971+886G>T		intron	N/A	NP_005763.3
	RCL1	NM_001286699.2		c.497+886G>T		intron	N/A	NP_001273628.1
	RCL1	NM_001286700.2		c.497+886G>T		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.971+886G>T		intron	N/A	ENSP00000371169.4
	RCL1	ENST00000448872.6	TSL:1	c.413+886G>T		intron	N/A	ENSP00000388096.2
	RCL1	ENST00000442869.5	TSL:3	c.497+886G>T		intron	N/A	ENSP00000412000.2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 85517 AN: 150332 Hom.: 24637 Cov.: 26

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.556 AC: 124861 AN: 224424 Hom.: 35091 AF XY: 0.549 AC XY: 69371 AN XY: 126462

African (AFR) AF: 0.540 AC: 4393 AN: 8134

American (AMR) AF: 0.496 AC: 15299 AN: 30852

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 5118 AN: 8226

East Asian (EAS) AF: 0.737 AC: 7604 AN: 10316

South Asian (SAS) AF: 0.421 AC: 15507 AN: 36852

European-Finnish (FIN) AF: 0.577 AC: 14548 AN: 25226

Middle Eastern (MID) AF: 0.561 AC: 667 AN: 1188

European-Non Finnish (NFE) AF: 0.597 AC: 56673 AN: 94916

Other (OTH) AF: 0.580 AC: 5052 AN: 8714

GnomAD4 genome AF: 0.569 AC: 85560 AN: 150438 Hom.: 24638 Cov.: 26 AF XY: 0.566 AC XY: 41510 AN XY: 73340

African (AFR) AF: 0.532 AC: 21745 AN: 40862

American (AMR) AF: 0.546 AC: 8268 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2147 AN: 3458

East Asian (EAS) AF: 0.746 AC: 3812 AN: 5112

South Asian (SAS) AF: 0.420 AC: 2001 AN: 4764

European-Finnish (FIN) AF: 0.575 AC: 5808 AN: 10106

Middle Eastern (MID) AF: 0.514 AC: 149 AN: 290

European-Non Finnish (NFE) AF: 0.590 AC: 39950 AN: 67734

Other (OTH) AF: 0.599 AC: 1247 AN: 2082

Alfa AF: 0.515 Hom.: 3287

Bravo AF: 0.571

Asia WGS AF: 0.545 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.042
DANN	Benign	0.42
PhyloP100		-2.0
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: rs462480; hg19: chr9-4850436; COSMIC: COSV63004721; COSMIC: COSV63004721;