Genetic Variant RRM1:n.38C>A (chr11-4094744-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000532710.5(RRM1):n.38C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 565,090 control chromosomes in the GnomAD database, including 22,073 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 0.22 ( 4586 hom., cov: 33)

Exomes 𝑓: 0.28 ( 17487 hom. )

Consequence

RRM1
ENST00000532710.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.795

Publications

54 publications found

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 Gene-Disease associations (from GenCC):

progressive external ophthalmoplegia with mitochondrial DNA deletions
Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6
Inheritance: AR, AD Classification: LIMITED Submitted by: G2P

RRM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM1	NM_001318064.1 link	c.-382C>A		5_prime_UTR_variant	Exon 1 of 18		NP_001304993.1	P23921B4E0I8
RRM1	NM_001033.5 link	c.-269C>A		upstream_gene_variant		ENST00000300738.10	NP_001024.1	P23921

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10 link	c.-269C>A		upstream_gene_variant		1	NM_001033.5	ENSP00000300738.5		P23921

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33859

AN:

152096

Hom.:

4587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0669

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.282

AC:

116514

AN:

412876

Hom.:

17487

Cov.:

AF XY:

0.289

AC XY:

62501

AN XY:

216126

show subpopulations

African (AFR)

AF:

0.0600

AC:

714

AN:

11902

American (AMR)

AF:

0.222

AC:

3907

AN:

17606

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

3447

AN:

12954

East Asian (EAS)

AF:

0.281

AC:

8375

AN:

29788

South Asian (SAS)

AF:

0.385

AC:

16041

AN:

41616

European-Finnish (FIN)

AF:

0.347

AC:

9522

AN:

27414

Middle Eastern (MID)

AF:

0.290

AC:

520

AN:

1792

European-Non Finnish (NFE)

AF:

0.275

AC:

67634

AN:

245722

Other (OTH)

AF:

0.264

AC:

6354

AN:

24082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3873

7745

11618

15490

19363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33861

AN:

152214

Hom.:

4586

Cov.:

AF XY:

0.229

AC XY:

17060

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0668

AC:

2778

AN:

41576

American (AMR)

AF:

0.230

AC:

3523

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

880

AN:

3466

East Asian (EAS)

AF:

0.290

AC:

1498

AN:

5162

South Asian (SAS)

AF:

0.377

AC:

1822

AN:

4830

European-Finnish (FIN)

AF:

0.352

AC:

3720

AN:

10580

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18928

AN:

67986

Other (OTH)

AF:

0.214

AC:

453

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1298

2597

3895

5194

6492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.256

Hom.:

16302

Bravo

AF:

0.199

Asia WGS

AF:

0.290

AC:

1008

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.9

(source)

DANN

Benign

0.52

PhyloP100

-0.80

PromoterAI

-0.051

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over