dbSNP rs12806698: 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

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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