rs183484

Positions:

• chr11-4119902-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001033.5(RRM1):​c.850C>A​(p.Arg284=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRM1	NM_001033.5	c.850C>A	p.Arg284=	synonymous_variant	9/19	ENST00000300738.10	NP_001024.1
RRM1	NM_001318064.1	c.559C>A	p.Arg187=	synonymous_variant	8/18		NP_001304993.1
RRM1	NM_001330193.1	c.184C>A	p.Arg62=	synonymous_variant	3/13		NP_001317122.1
RRM1	NM_001318065.1	c.-207C>A		5_prime_UTR_variant	3/13		NP_001304994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10	c.850C>A	p.Arg284=	synonymous_variant	9/19	1	NM_001033.5	ENSP00000300738	P1

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

GnomAD3 exomes AF: 0.453 AC: 112733 AN: 249046 Hom.: 27373 AF XY: 0.457 AC XY: 61509 AN XY: 134662

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 SAS exome AF: 0.356

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

Gnomad4 AFR exome AF: 0.0815

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.472

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

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.419

Alfa AF: 0.471 Hom.: 11423

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	13
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs183484; hg19: chr11-4141132; COSMIC: COSV56163366; COSMIC: COSV56163366;