dbSNP rs1056892: CBR3:p.Val244Met (chr21-36146408-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001236.4(CBR3):c.730G>A(p.Val244Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,613,776 control chromosomes in the GnomAD database, including 112,002 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V244L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.39 ( 11709 hom., cov: 32)

Exomes 𝑓: 0.37 ( 100293 hom. )

Consequence

CBR3
NM_001236.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87

Publications

130 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 links:

CBR3-AS1 (HGNC:43664): (CBR3 antisense RNA 1)

CBR3-AS1 links:

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=0.001534909).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBR3	NM_001236.4	MANE Select	c.730G>A	p.Val244Met	missense	Exon 3 of 3	NP_001227.1	O75828
CBR3-AS1	NR_038892.1		n.93-53C>T		intron	N/A
CBR3-AS1	NR_038893.1		n.93-53C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBR3	ENST00000290354.6	TSL:1 MANE Select	c.730G>A	p.Val244Met	missense	Exon 3 of 3	ENSP00000290354.5	O75828
CBR3-AS1	ENST00000432988.1	TSL:1	n.3959C>T		non_coding_transcript_exon	Exon 2 of 3
CBR3-AS1	ENST00000427491.4	TSL:1	n.145-53C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58757

AN:

151888

Hom.:

11707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.367

AC:

92349

AN:

251384

AF XY:

0.374

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.367

AC:

535955

AN:

1461772

Hom.:

100293

Cov.:

AF XY:

0.370

AC XY:

269176

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.481

AC:

16096

AN:

33476

American (AMR)

AF:

0.275

AC:

12319

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

10583

AN:

26130

East Asian (EAS)

AF:

0.396

AC:

15704

AN:

39700

South Asian (SAS)

AF:

0.478

AC:

41240

AN:

86254

European-Finnish (FIN)

AF:

0.311

AC:

16610

AN:

53416

Middle Eastern (MID)

AF:

0.454

AC:

2617

AN:

5768

European-Non Finnish (NFE)

AF:

0.358

AC:

397902

AN:

1111914

Other (OTH)

AF:

0.379

AC:

22884

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

20083

40167

60250

80334

100417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12872

25744

38616

51488

64360

<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:

0.387

AC:

58788

AN:

152004

Hom.:

11709

Cov.:

AF XY:

0.384

AC XY:

28566

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.468

AC:

19406

AN:

41438

American (AMR)

AF:

0.296

AC:

4512

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

1393

AN:

3470

East Asian (EAS)

AF:

0.404

AC:

2089

AN:

5170

South Asian (SAS)

AF:

0.499

AC:

2406

AN:

4822

European-Finnish (FIN)

AF:

0.329

AC:

3478

AN:

10576

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.357

AC:

24259

AN:

67956

Other (OTH)

AF:

0.362

AC:

765

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1796

3591

5387

7182

8978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.368

Hom.:

41301

Bravo

AF:

0.387

TwinsUK

AF:

0.354

AC:

1312

ALSPAC

AF:

0.360

AC:

1388

ESP6500AA

AF:

0.475

AC:

2092

ESP6500EA

AF:

0.360

AC:

3094

ExAC

AF:

0.374

AC:

45404

Asia WGS

AF:

0.436

AC:

1517

AN:

3478

EpiCase

AF:

0.356

EpiControl

AF:

0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PhyloP100

2.9

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.63

REVEL

Benign

0.084

Sift

Benign

0.069

Sift4G

Benign

0.077

Polyphen

0.62

Vest4

0.038

MPC

0.35

ClinPred

0.010

GERP RS

0.55

Varity_R

0.094

gMVP

0.33

Mutation Taster

=65/35

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over