rs8133052

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001236.4(CBR3):​c.11G>A​(p.Cys4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,496,066 control chromosomes in the GnomAD database, including 148,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12552 hom., cov: 34)
Exomes 𝑓: 0.45 ( 135536 hom. )

Consequence

CBR3
NM_001236.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.163

Publications

76 publications found
Variant links:
Genes affected
CBR3 (HGNC:1549): (carbonyl reductase 3) Carbonyl reductase 3 catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols. The enzyme is classified as a monomeric NADPH-dependent oxidoreductase. CBR3 contains three exons spanning 11.2 kilobases and is closely linked to another carbonyl reductase gene - CBR1. [provided by RefSeq, Jul 2008]
CBR3-AS1 (HGNC:43664): (CBR3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.9779801E-4).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBR3NM_001236.4 linkc.11G>A p.Cys4Tyr missense_variant Exon 1 of 3 ENST00000290354.6 NP_001227.1
CBR3XM_011529772.3 linkc.11G>A p.Cys4Tyr missense_variant Exon 1 of 3 XP_011528074.1
CBR3-AS1NR_038892.1 linkn.193-1442C>T intron_variant Intron 2 of 3
CBR3-AS1NR_038893.1 linkn.193-2129C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBR3ENST00000290354.6 linkc.11G>A p.Cys4Tyr missense_variant Exon 1 of 3 1 NM_001236.4 ENSP00000290354.5 O75828

Frequencies

GnomAD3 genomes
AF:
0.397
AC:
60356
AN:
152018
Hom.:
12544
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.282
Gnomad AMI
AF:
0.311
Gnomad AMR
AF:
0.474
Gnomad ASJ
AF:
0.381
Gnomad EAS
AF:
0.438
Gnomad SAS
AF:
0.301
Gnomad FIN
AF:
0.407
Gnomad MID
AF:
0.404
Gnomad NFE
AF:
0.453
Gnomad OTH
AF:
0.434
GnomAD2 exomes
AF:
0.439
AC:
49376
AN:
112494
AF XY:
0.436
show subpopulations
Gnomad AFR exome
AF:
0.296
Gnomad AMR exome
AF:
0.492
Gnomad ASJ exome
AF:
0.400
Gnomad EAS exome
AF:
0.452
Gnomad FIN exome
AF:
0.431
Gnomad NFE exome
AF:
0.473
Gnomad OTH exome
AF:
0.446
GnomAD4 exome
AF:
0.446
AC:
599969
AN:
1343934
Hom.:
135536
Cov.:
48
AF XY:
0.444
AC XY:
291464
AN XY:
657002
show subpopulations
African (AFR)
AF:
0.280
AC:
8321
AN:
29682
American (AMR)
AF:
0.486
AC:
14402
AN:
29632
Ashkenazi Jewish (ASJ)
AF:
0.383
AC:
8004
AN:
20908
East Asian (EAS)
AF:
0.454
AC:
16058
AN:
35336
South Asian (SAS)
AF:
0.318
AC:
22177
AN:
69798
European-Finnish (FIN)
AF:
0.422
AC:
17920
AN:
42480
Middle Eastern (MID)
AF:
0.358
AC:
1899
AN:
5298
European-Non Finnish (NFE)
AF:
0.462
AC:
487342
AN:
1055090
Other (OTH)
AF:
0.428
AC:
23846
AN:
55710
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
17918
35836
53754
71672
89590
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
15004
30008
45012
60016
75020
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.397
AC:
60403
AN:
152132
Hom.:
12552
Cov.:
34
AF XY:
0.396
AC XY:
29413
AN XY:
74368
show subpopulations
African (AFR)
AF:
0.282
AC:
11722
AN:
41538
American (AMR)
AF:
0.475
AC:
7257
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.381
AC:
1321
AN:
3468
East Asian (EAS)
AF:
0.438
AC:
2257
AN:
5156
South Asian (SAS)
AF:
0.301
AC:
1451
AN:
4822
European-Finnish (FIN)
AF:
0.407
AC:
4308
AN:
10586
Middle Eastern (MID)
AF:
0.404
AC:
118
AN:
292
European-Non Finnish (NFE)
AF:
0.453
AC:
30769
AN:
67966
Other (OTH)
AF:
0.434
AC:
917
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1914
3828
5741
7655
9569
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
568
1136
1704
2272
2840
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.448
Hom.:
42651
Bravo
AF:
0.401
TwinsUK
AF:
0.471
AC:
1746
ALSPAC
AF:
0.466
AC:
1797
ESP6500AA
AF:
0.270
AC:
1102
ESP6500EA
AF:
0.425
AC:
3407
ExAC
AF:
0.328
AC:
34990
Asia WGS
AF:
0.355
AC:
1232
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.010
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.35
T
MetaRNN
Benign
0.00020
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.040
N
PhyloP100
0.16
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.090
Sift
Benign
0.37
T
Sift4G
Benign
0.39
T
Polyphen
0.0
B
Vest4
0.045
MPC
0.33
ClinPred
0.011
T
GERP RS
2.5
PromoterAI
0.081
Neutral
Varity_R
0.12
gMVP
0.41
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs8133052; hg19: chr21-37507501; COSMIC: COSV51740640; COSMIC: COSV51740640; API