chr11-4122462-T-A

Variant names:

• chr11-4122462-T-A
• rs232045
• NM_001033.5:c.1118+242T>A

Variant summary

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

The NM_001033.5(RRM1):​c.1118+242T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 152,284 control chromosomes in the GnomAD database, including 66,014 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 0.93 (66014 hom., cov: 32)
• Consequence: RRM1 NM_001033.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.943 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.1118+242T>A		intron	N/A	NP_001024.1	P23921
	RRM1	NM_001318064.1		c.827+242T>A		intron	N/A	NP_001304993.1	B4E0I8
	RRM1	NM_001330193.1		c.452+242T>A		intron	N/A	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.1118+242T>A		intron	N/A	ENSP00000300738.5	P23921
	RRM1	ENST00000854928.1		c.1049+242T>A		intron	N/A	ENSP00000524987.1
	RRM1	ENST00000854929.1		c.1118+242T>A		intron	N/A	ENSP00000524988.1

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141631 AN: 152166 Hom.: 65988 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.925

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.931 AC: 141712 AN: 152284 Hom.: 66014 Cov.: 32 AF XY: 0.930 AC XY: 69290 AN XY: 74470

African (AFR) AF: 0.882 AC: 36620 AN: 41532

American (AMR) AF: 0.952 AC: 14578 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3257 AN: 3468

East Asian (EAS) AF: 0.937 AC: 4865 AN: 5192

South Asian (SAS) AF: 0.957 AC: 4620 AN: 4830

European-Finnish (FIN) AF: 0.957 AC: 10144 AN: 10604

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64578 AN: 68036

Other (OTH) AF: 0.921 AC: 1944 AN: 2110

Alfa AF: 0.936 Hom.: 8279

Bravo AF: 0.927

Asia WGS AF: 0.934 AC: 3250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-0.10
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: rs232045; hg19: chr11-4143692;