rs12806698

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RRM1	NM_001318064.1	c.-382C>A		5_prime_UTR_variant	1/18		NP_001304993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000532710.5	n.38C>A		non_coding_transcript_exon_variant	1/3	4

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

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.264

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

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.214

Alfa AF: 0.265 Hom.: 6266

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
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12806698; hg19: chr11-4115974;