chr9-4819421-G-A

Variant names:

• chr9-4819421-G-A
• rs377186
• NM_005772.5:c.137-4127G>A

Variant summary

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

The NM_005772.5(RCL1):​c.137-4127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,022 control chromosomes in the GnomAD database, including 12,314 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 0.39 (12314 hom., cov: 33)
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.137-4127G>A		intron_variant	Intron 1 of 8	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2	c.-90-13733G>A		intron_variant	Intron 1 of 6		NP_001273628.1
RCL1	NM_001286700.2	c.-162-4127G>A		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.137-4127G>A		intron_variant	Intron 1 of 8	1	NM_005772.5	ENSP00000371169.4
RCL1	ENST00000442869.5	c.-162-4127G>A		intron_variant	Intron 1 of 7	3		ENSP00000412000.2
RCL1	ENST00000381732.3	c.137-4127G>A		intron_variant	Intron 1 of 2	2		ENSP00000371151.3
RCL1	ENST00000473230.1	n.142-4127G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58838 AN: 151904 Hom.: 12316 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.387 AC: 58851 AN: 152022 Hom.: 12314 Cov.: 33 AF XY: 0.393 AC XY: 29178 AN XY: 74308

African (AFR) AF: 0.216 AC: 8941 AN: 41462

American (AMR) AF: 0.441 AC: 6746 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5174

South Asian (SAS) AF: 0.487 AC: 2345 AN: 4818

European-Finnish (FIN) AF: 0.509 AC: 5359 AN: 10536

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31349 AN: 67970

Other (OTH) AF: 0.395 AC: 834 AN: 2114

Alfa AF: 0.433 Hom.: 57071

Bravo AF: 0.378

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.034
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: rs377186; hg19: chr9-4819421;