Variant rs9937 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001033.5(RRM1):c.2223A>G(p.Thr741=) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

Variant links:

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 links:

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

RRM1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE
RRM1	NM_001033.5 linkuse as main transcript	c.2223A>G	p.Thr741=	synonymous_variant	19/19	ENST00000300738.10
RRM1	NM_001318064.1 linkuse as main transcript	c.1932A>G	p.Thr644=	synonymous_variant	18/18
RRM1	NM_001330193.1 linkuse as main transcript	c.1557A>G	p.Thr519=	synonymous_variant	13/13
RRM1	NM_001318065.1 linkuse as main transcript	c.1209A>G	p.Thr403=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM1	ENST00000300738.10 linkuse as main transcript	c.2223A>G	p.Thr741=	synonymous_variant	19/19	1	NM_001033.5	P1
RRM1-AS1	ENST00000529323.1 linkuse as main transcript	n.31T>C		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61833

AN:

151724

Hom.:

14561

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.461

AC:

113624

AN:

246406

Hom.:

27694

AF XY:

0.464

AC XY:

61932

AN XY:

133416

show subpopulations

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 SAS exome

AF:

0.367

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.:

AF XY:

0.510

AC XY:

363856

AN XY:

713600

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.503

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.407

AC:

61820

AN:

151842

Hom.:

14553

Cov.:

AF XY:

0.402

AC XY:

29788

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.515

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.455

Gnomad4 NFE

AF:

0.537

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.478

Hom.:

10717

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

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over