Variant 11-4138227-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001033.5(RRM1):c.2223A>T(p.Thr741=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RRM1
NM_001033.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

Variant links:

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 links:

RRM1-AS1 (HGNC:40512): (RRM1 antisense RNA 1)

RRM1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP7

Synonymous conserved (PhyloP=-0.447 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RRM1	NM_001033.5 linkuse as main transcript	c.2223A>T	p.Thr741=	synonymous_variant	19/19	ENST00000300738.10
RRM1	NM_001318064.1 linkuse as main transcript	c.1932A>T	p.Thr644=	synonymous_variant	18/18
RRM1	NM_001330193.1 linkuse as main transcript	c.1557A>T	p.Thr519=	synonymous_variant	13/13
RRM1	NM_001318065.1 linkuse as main transcript	c.1209A>T	p.Thr403=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRM1	ENST00000300738.10 linkuse as main transcript	c.2223A>T	p.Thr741=	synonymous_variant	19/19	1	NM_001033.5	P1
RRM1-AS1	ENST00000529323.1 linkuse as main transcript	n.31T>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1441222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718198

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over