rs9937

Variant names:

• chr11-4138227-A-G
• rs9937
• NM_001033.5:c.2223A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-4138227-A-G
• chr11-4138227-A-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.2223A>G​(p.Thr741Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,582,966 control chromosomes in the GnomAD database, including 208,637 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 0.41 (14553 hom., cov: 29)
  • Exomes 𝑓: 0.51 (194084 hom.)
• Consequence: RRM1 NM_001033.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 37 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=-0.37).
• BP7: Synonymous conserved (PhyloP=-0.447 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM1	NM_001033.5	c.2223A>G	p.Thr741Thr	synonymous_variant	Exon 19 of 19	ENST00000300738.10	NP_001024.1
RRM1	NM_001318064.1	c.1932A>G	p.Thr644Thr	synonymous_variant	Exon 18 of 18		NP_001304993.1
RRM1	NM_001330193.1	c.1557A>G	p.Thr519Thr	synonymous_variant	Exon 13 of 13		NP_001317122.1
RRM1	NM_001318065.1	c.1209A>G	p.Thr403Thr	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.2223A>G	p.Thr741Thr	synonymous_variant	Exon 19 of 19	1	NM_001033.5	ENSP00000300738.5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61833 AN: 151724 Hom.: 14561 Cov.: 29

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.442

GnomAD2 exomes AF: 0.461 AC: 113624 AN: 246406 AF XY: 0.464

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.539

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.513 AC: 733925 AN: 1431124 Hom.: 194084 Cov.: 26 AF XY: 0.510 AC XY: 363856 AN XY: 713600

African (AFR) AF: 0.141 AC: 4640 AN: 32912

American (AMR) AF: 0.458 AC: 20004 AN: 43684

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 12922 AN: 25694

East Asian (EAS) AF: 0.423 AC: 16651 AN: 39370

South Asian (SAS) AF: 0.367 AC: 31170 AN: 84910

European-Finnish (FIN) AF: 0.470 AC: 25033 AN: 53252

Middle Eastern (MID) AF: 0.446 AC: 2537 AN: 5694

European-Non Finnish (NFE) AF: 0.546 AC: 592597 AN: 1086302

Other (OTH) AF: 0.478 AC: 28371 AN: 59306

GnomAD4 genome AF: 0.407 AC: 61820 AN: 151842 Hom.: 14553 Cov.: 29 AF XY: 0.402 AC XY: 29788 AN XY: 74180

African (AFR) AF: 0.159 AC: 6577 AN: 41478

American (AMR) AF: 0.453 AC: 6911 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1785 AN: 3464

East Asian (EAS) AF: 0.384 AC: 1973 AN: 5140

South Asian (SAS) AF: 0.376 AC: 1809 AN: 4806

European-Finnish (FIN) AF: 0.455 AC: 4788 AN: 10534

Middle Eastern (MID) AF: 0.431 AC: 125 AN: 290

European-Non Finnish (NFE) AF: 0.537 AC: 36456 AN: 67858

Other (OTH) AF: 0.438 AC: 924 AN: 2110

Alfa AF: 0.481 Hom.: 38259

Bravo AF: 0.400

Asia WGS AF: 0.346 AC: 1204 AN: 3478

EpiCase AF: 0.540

EpiControl AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.89
PhyloP100		-0.45
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: rs9937; hg19: chr11-4159457; COSMIC: COSV56163380;