rs1042858

chr11-4138236-G-Achr11-4138236-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001033.5(RRM1):c.2232G>A(p.Ala744=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,595,348 control chromosomes in the GnomAD database, including 673,027 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 0.88 (59077 hom., cov: 30)
  • Exomes 𝑓: 0.92 (613950 hom.)
• Consequence: RRM1 NM_001033.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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-AS1 (HGNC:40512): (RRM1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRM1	NM_001033.5	c.2232G>A	p.Ala744=	synonymous_variant	19/19	ENST00000300738.10
RRM1	NM_001318064.1	c.1941G>A	p.Ala647=	synonymous_variant	18/18
RRM1	NM_001330193.1	c.1566G>A	p.Ala522=	synonymous_variant	13/13
RRM1	NM_001318065.1	c.1218G>A	p.Ala406=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM1	ENST00000300738.10	c.2232G>A	p.Ala744=	synonymous_variant	19/19	1	NM_001033.5	P1
RRM1-AS1	ENST00000529323.1	n.22C>T		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133563 AN: 151784 Hom.: 59074 Cov.: 30

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.881

GnomAD3 exomes AF: 0.889 AC: 221103 AN: 248604 Hom.: 98902 AF XY: 0.898 AC XY: 120743 AN XY: 134530

Gnomad AFR exome AF: 0.813

Gnomad AMR exome AF: 0.813

Gnomad ASJ exome AF: 0.919

Gnomad EAS exome AF: 0.736

Gnomad SAS exome AF: 0.941

Gnomad FIN exome AF: 0.899

Gnomad NFE exome AF: 0.929

Gnomad OTH exome AF: 0.894

GnomAD4 exome AF: 0.921 AC: 1329872 AN: 1443446 Hom.: 613950 Cov.: 27 AF XY: 0.923 AC XY: 663716 AN XY: 719328

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.916

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.942

Gnomad4 FIN exome AF: 0.904

Gnomad4 NFE exome AF: 0.935

Gnomad4 OTH exome AF: 0.902

GnomAD4 genome AF: 0.880 AC: 133605 AN: 151902 Hom.: 59077 Cov.: 30 AF XY: 0.875 AC XY: 64958 AN XY: 74208

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.874

Alfa AF: 0.910 Hom.: 32460

Bravo AF: 0.870

EpiCase AF: 0.930

EpiControl AF: 0.928

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	6.8
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1042858; hg19: chr11-4159466; COSMIC: COSV56164351;