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GeneBe

11-4127223-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001033.5(RRM1):c.1659C>T(p.Tyr553=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,605,048 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 28 hom. )

Consequence

RRM1
NM_001033.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0880
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-4127223-C-T is Benign according to our data. Variant chr11-4127223-C-T is described in ClinVar as [Benign]. Clinvar id is 719475.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.088 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00199 (2891/1452816) while in subpopulation EAS AF= 0.0221 (875/39646). AF 95% confidence interval is 0.0209. There are 28 homozygotes in gnomad4_exome. There are 1588 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 315 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RRM1NM_001033.5 linkuse as main transcriptc.1659C>T p.Tyr553= synonymous_variant 14/19 ENST00000300738.10
RRM1NM_001318064.1 linkuse as main transcriptc.1368C>T p.Tyr456= synonymous_variant 13/18
RRM1NM_001330193.1 linkuse as main transcriptc.993C>T p.Tyr331= synonymous_variant 8/13
RRM1NM_001318065.1 linkuse as main transcriptc.645C>T p.Tyr215= synonymous_variant 8/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRM1ENST00000300738.10 linkuse as main transcriptc.1659C>T p.Tyr553= synonymous_variant 14/191 NM_001033.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00207
AC:
315
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0139
Gnomad SAS
AF:
0.00973
Gnomad FIN
AF:
0.0123
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000764
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00380
AC:
907
AN:
238582
Hom.:
8
AF XY:
0.00386
AC XY:
499
AN XY:
129188
show subpopulations
Gnomad AFR exome
AF:
0.000187
Gnomad AMR exome
AF:
0.0000964
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0161
Gnomad SAS exome
AF:
0.00847
Gnomad FIN exome
AF:
0.0119
Gnomad NFE exome
AF:
0.000948
Gnomad OTH exome
AF:
0.00348
GnomAD4 exome
AF:
0.00199
AC:
2891
AN:
1452816
Hom.:
28
Cov.:
31
AF XY:
0.00220
AC XY:
1588
AN XY:
722642
show subpopulations
Gnomad4 AFR exome
AF:
0.000243
Gnomad4 AMR exome
AF:
0.000142
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0221
Gnomad4 SAS exome
AF:
0.00738
Gnomad4 FIN exome
AF:
0.0126
Gnomad4 NFE exome
AF:
0.000529
Gnomad4 OTH exome
AF:
0.00197
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00207
AC:
315
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.00262
AC XY:
195
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0139
Gnomad4 SAS
AF:
0.00974
Gnomad4 FIN
AF:
0.0123
Gnomad4 NFE
AF:
0.000764
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000734
Hom.:
0
Bravo
AF:
0.00121
Asia WGS
AF:
0.0150
AC:
53
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 02, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
8.3
Dann
Benign
0.40
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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.

Other links and lift over

dbSNP: rs138097785; hg19: chr11-4148453; COSMIC: COSV56162954; COSMIC: COSV56162954; API