9-4850436-G-T

Position:

• chr9-4850436-G-T

Variant summary

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

The ENST00000381750.9(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 ENST00000381750.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCL1	NM_005772.5	c.971+886G>T		intron_variant		ENST00000381750.9	NP_005763.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.971+886G>T		intron_variant		1	NM_005772.5	ENSP00000371169.4

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

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.496

Gnomad4 ASJ exome AF: 0.622

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.580

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

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.599

Alfa AF: 0.514 Hom.: 3161

Bravo AF: 0.571

Asia WGS AF: 0.545 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.042
DANN	Benign	0.42

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: rs462480; hg19: chr9-4850436; COSMIC: COSV63004721; COSMIC: COSV63004721;