rs1042927

Variant names:

• chr11-4138699-C-A
• rs1042927
• NM_001033.5:c.*316C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033.5. 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_001033.5	MANE Select	c.*316C>A		3_prime_UTR	Exon 19 of 19	NP_001024.1	P23921
	RRM1	NM_001318064.1		c.*316C>A		3_prime_UTR	Exon 18 of 18	NP_001304993.1	B4E0I8
	RRM1	NM_001330193.1		c.*316C>A		3_prime_UTR	Exon 13 of 13	NP_001317122.1	E9PL69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRM1	ENST00000300738.10	TSL:1 MANE Select	c.*316C>A		3_prime_UTR	Exon 19 of 19	ENSP00000300738.5	P23921
	RRM1	ENST00000854928.1		c.*316C>A		3_prime_UTR	Exon 19 of 19	ENSP00000524987.1
	RRM1	ENST00000532170.5	TSL:2	n.*2571C>A		non_coding_transcript_exon	Exon 20 of 20	ENSP00000435656.1	E9PJ62

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

African (AFR) AF: 0.803 AC: 3390 AN: 4220

American (AMR) AF: 0.823 AC: 2383 AN: 2896

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 4792 AN: 5250

East Asian (EAS) AF: 0.802 AC: 8998 AN: 11222

South Asian (SAS) AF: 0.932 AC: 1007 AN: 1080

European-Finnish (FIN) AF: 0.893 AC: 1057 AN: 1184

Middle Eastern (MID) AF: 0.841 AC: 439 AN: 522

European-Non Finnish (NFE) AF: 0.927 AC: 55400 AN: 59780

Other (OTH) AF: 0.896 AC: 6561 AN: 7324

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

African (AFR) AF: 0.812 AC: 33684 AN: 41506

American (AMR) AF: 0.855 AC: 13075 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3178 AN: 3472

East Asian (EAS) AF: 0.753 AC: 3888 AN: 5160

South Asian (SAS) AF: 0.933 AC: 4491 AN: 4812

European-Finnish (FIN) AF: 0.886 AC: 9374 AN: 10576

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63342 AN: 68012

Other (OTH) AF: 0.872 AC: 1841 AN: 2112

Alfa AF: 0.906 Hom.: 169602

Bravo AF: 0.870

Asia WGS AF: 0.787 AC: 2739 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.34
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042927; hg19: chr11-4159929;