rs1042927

Positions:

• chr11-4138699-C-A
• chr11-4138699-C-G
• chr11-4138699-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033.5(RRM1):​c.*316C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 245,632 control chromosomes in the GnomAD database, including 97,056 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 0.88 (59187 hom., cov: 31)
  • Exomes 𝑓: 0.90 (37869 hom.)
• Consequence: RRM1 NM_001033.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRM1	NM_001033.5	c.*316C>A		3_prime_UTR_variant	19/19	ENST00000300738.10	NP_001024.1
RRM1	NM_001318064.1	c.*316C>A		3_prime_UTR_variant	18/18		NP_001304993.1
RRM1	NM_001330193.1	c.*316C>A		3_prime_UTR_variant	13/13		NP_001317122.1
RRM1	NM_001318065.1	c.*316C>A		3_prime_UTR_variant	13/13		NP_001304994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10	c.*316C>A		3_prime_UTR_variant	19/19	1	NM_001033.5	ENSP00000300738.5

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133816 AN: 152036 Hom.: 59184 Cov.: 31

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.879

GnomAD4 exome AF: 0.899 AC: 84027 AN: 93478 Hom.: 37869 Cov.: 0 AF XY: 0.901 AC XY: 39959 AN XY: 44336

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.913

Gnomad4 EAS exome AF: 0.802

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.896

GnomAD4 genome AF: 0.880 AC: 133858 AN: 152154 Hom.: 59187 Cov.: 31 AF XY: 0.876 AC XY: 65125 AN XY: 74384

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.872

Alfa AF: 0.914 Hom.: 58380

Bravo AF: 0.870

Asia WGS AF: 0.787 AC: 2739 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1042927; hg19: chr11-4159929;