rs232045

chr11-4122462-T-Achr11-4122462-T-Cchr11-4122462-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRM1	NM_001033.5	c.1118+242T>A		intron_variant		ENST00000300738.10
RRM1	NM_001318064.1	c.827+242T>A		intron_variant
RRM1	NM_001318065.1	c.104+242T>A		intron_variant
RRM1	NM_001330193.1	c.452+242T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM1	ENST00000300738.10	c.1118+242T>A		intron_variant		1	NM_001033.5	P1

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

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.921

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.66

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: rs232045; hg19: chr11-4143692;