rs12806698

Variant names:

• chr11-4094744-C-A
• rs12806698
• NM_001318064.1:c.-382C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-4094744-C-A
• chr11-4094744-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318064.1(RRM1):​c.-382C>A variant causes a 5 prime UTR 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 NM_001318064.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• Publications: 54 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 Gene-Disease associations (from GenCC):

• progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, G2P
• progressive external ophthalmoplegia with mitochondrial DNA deletions

  Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318064.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM1	NM_001318064.1		c.-382C>A		5_prime_UTR	Exon 1 of 18	NP_001304993.1	B4E0I8
	RRM1	NM_001033.5	MANE Select	c.-269C>A		upstream_gene	N/A	NP_001024.1	P23921

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM1	ENST00000532710.5	TSL:4	n.38C>A		non_coding_transcript_exon	Exon 1 of 3
	RRM1	ENST00000300738.10	TSL:1 MANE Select	c.-269C>A		upstream_gene	N/A	ENSP00000300738.5	P23921
	RRM1	ENST00000854928.1		c.-269C>A		upstream_gene	N/A	ENSP00000524987.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33859 AN: 152096 Hom.: 4587 Cov.: 33

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.: 2 AF XY: 0.289 AC XY: 62501 AN XY: 216126

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

GnomAD4 genome AF: 0.222 AC: 33861 AN: 152214 Hom.: 4586 Cov.: 33 AF XY: 0.229 AC XY: 17060 AN XY: 74406

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: 73 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18928 AN: 67986

Other (OTH) AF: 0.214 AC: 453 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		-0.80
PromoterAI		-0.051	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12806698; hg19: chr11-4115974;