rs1042858

Variant names:

• chr11-4138236-G-A
• rs1042858
• NM_001033.5:c.2232G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-4138236-G-A
• chr11-4138236-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001033.5(RRM1):​c.2232G>A​(p.Ala744Ala) 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
• Publications: 40 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-AS1 (HGNC:40512): (RRM1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RRM1	NM_001033.5	c.2232G>A	p.Ala744Ala	synonymous_variant	Exon 19 of 19	ENST00000300738.10	NP_001024.1
RRM1	NM_001318064.1	c.1941G>A	p.Ala647Ala	synonymous_variant	Exon 18 of 18		NP_001304993.1
RRM1	NM_001330193.1	c.1566G>A	p.Ala522Ala	synonymous_variant	Exon 13 of 13		NP_001317122.1
RRM1	NM_001318065.1	c.1218G>A	p.Ala406Ala	synonymous_variant	Exon 13 of 13		NP_001304994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10	c.2232G>A	p.Ala744Ala	synonymous_variant	Exon 19 of 19	1	NM_001033.5	ENSP00000300738.5

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

GnomAD2 exomes AF: 0.889 AC: 221103 AN: 248604 AF XY: 0.898

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 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

African (AFR) AF: 0.808 AC: 26712 AN: 33056

American (AMR) AF: 0.819 AC: 36124 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 23761 AN: 25930

East Asian (EAS) AF: 0.784 AC: 30954 AN: 39478

South Asian (SAS) AF: 0.942 AC: 80539 AN: 85538

European-Finnish (FIN) AF: 0.904 AC: 48213 AN: 53328

Middle Eastern (MID) AF: 0.852 AC: 4880 AN: 5726

European-Non Finnish (NFE) AF: 0.935 AC: 1024818 AN: 1096564

Other (OTH) AF: 0.902 AC: 53871 AN: 59702

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

African (AFR) AF: 0.811 AC: 33590 AN: 41406

American (AMR) AF: 0.854 AC: 13048 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3172 AN: 3466

East Asian (EAS) AF: 0.753 AC: 3880 AN: 5150

South Asian (SAS) AF: 0.933 AC: 4494 AN: 4818

European-Finnish (FIN) AF: 0.885 AC: 9349 AN: 10558

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.931 AC: 63256 AN: 67932

Other (OTH) AF: 0.874 AC: 1840 AN: 2106

Alfa AF: 0.904 Hom.: 136793

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
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs1042858; hg19: chr11-4159466; COSMIC: COSV56164351;