rs720106

chr11-4118748-T-C

Variant summary

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

The NM_001033.5(RRM1):c.792+287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 152,296 control chromosomes in the GnomAD database, including 265 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 0.041 (265 hom., cov: 32)
• Consequence: RRM1 NM_001033.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRM1	NM_001033.5	c.792+287T>C		intron_variant		ENST00000300738.10
RRM1	NM_001318064.1	c.501+287T>C		intron_variant
RRM1	NM_001318065.1	c.-265+287T>C		intron_variant
RRM1	NM_001330193.1	c.126+287T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM1	ENST00000300738.10	c.792+287T>C		intron_variant		1	NM_001033.5	P1

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6153 AN: 152178 Hom.: 260 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0405 AC: 6174 AN: 152296 Hom.: 265 Cov.: 32 AF XY: 0.0448 AC XY: 3333 AN XY: 74472

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0701

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0328 Hom.: 100

Bravo AF: 0.0446

Asia WGS AF: 0.147 AC: 511 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.4
Dann	Benign	0.72

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: rs720106; hg19: chr11-4139978;