rs183484

Variant names:

• chr11-4119902-C-A
• rs183484
• NM_001033.5:c.850C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-4119902-C-A
• chr11-4119902-C-G
• chr11-4119902-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001033.5(RRM1):​c.850C>A​(p.Arg284Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.497 in 1,592,452 control chromosomes in the GnomAD database, including 207,237 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 (14144 hom., cov: 31)
  • Exomes 𝑓: 0.51 (193093 hom.)
• Consequence: RRM1 NM_001033.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 33 publications found

Genes affected

RRM1 (HGNC:10451): (ribonucleotide reductase catalytic subunit M1) This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

RRM1 Gene-Disease associations (from GenCC):

• progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, G2P
• progressive external ophthalmoplegia with mitochondrial DNA deletions

  Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM1	NM_001033.5	MANE Select	c.850C>A	p.Arg284Arg	synonymous	Exon 9 of 19	NP_001024.1	P23921
	RRM1	NM_001318064.1		c.559C>A	p.Arg187Arg	synonymous	Exon 8 of 18	NP_001304993.1	B4E0I8
	RRM1	NM_001330193.1		c.184C>A	p.Arg62Arg	synonymous	Exon 3 of 13	NP_001317122.1	E9PL69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM1	ENST00000300738.10	TSL:1 MANE Select	c.850C>A	p.Arg284Arg	synonymous	Exon 9 of 19	ENSP00000300738.5	P23921
	RRM1	ENST00000854928.1		c.850C>A	p.Arg284Arg	synonymous	Exon 9 of 19	ENSP00000524987.1
	RRM1	ENST00000854929.1		c.850C>A	p.Arg284Arg	synonymous	Exon 9 of 18	ENSP00000524988.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59190 AN: 151586 Hom.: 14153 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.423

GnomAD2 exomes AF: 0.453 AC: 112733 AN: 249046 AF XY: 0.457

Gnomad AFR exome AF: 0.0868

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.536

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.509 AC: 732987 AN: 1440750 Hom.: 193093 Cov.: 28 AF XY: 0.506 AC XY: 362987 AN XY: 717766

African (AFR) AF: 0.0815 AC: 2714 AN: 33320

American (AMR) AF: 0.448 AC: 19707 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 12923 AN: 25962

East Asian (EAS) AF: 0.422 AC: 16673 AN: 39504

South Asian (SAS) AF: 0.360 AC: 30711 AN: 85350

European-Finnish (FIN) AF: 0.470 AC: 25069 AN: 53368

Middle Eastern (MID) AF: 0.440 AC: 2514 AN: 5716

European-Non Finnish (NFE) AF: 0.543 AC: 594467 AN: 1093854

Other (OTH) AF: 0.472 AC: 28209 AN: 59706

GnomAD4 genome AF: 0.390 AC: 59163 AN: 151702 Hom.: 14144 Cov.: 31 AF XY: 0.385 AC XY: 28549 AN XY: 74092

African (AFR) AF: 0.100 AC: 4142 AN: 41310

American (AMR) AF: 0.445 AC: 6790 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1996 AN: 5164

South Asian (SAS) AF: 0.375 AC: 1804 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4797 AN: 10470

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36371 AN: 67912

Other (OTH) AF: 0.419 AC: 880 AN: 2102

Alfa AF: 0.472 Hom.: 40049

Bravo AF: 0.379

Asia WGS AF: 0.338 AC: 1175 AN: 3478

EpiCase AF: 0.536

EpiControl AF: 0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		5.8
Mutation Taster		=8/92	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs183484; hg19: chr11-4141132; COSMIC: COSV56163366; COSMIC: COSV56163366;