dbSNP rs2835285: CBR3:p.Val93Ile (chr21-36135469-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001236.4(CBR3):c.277G>A(p.Val93Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,611,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 0.0000066 ( 0 hom., cov: 35)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CBR3
NM_001236.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.25

Publications

5 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07134992).

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.277G>A	p.Val93Ile	missense	Exon 1 of 3	NP_001227.1	O75828
CBR3-AS1	NR_038892.1		n.193-1708C>T		intron	N/A
CBR3-AS1	NR_038893.1		n.193-2395C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBR3	ENST00000290354.6	TSL:1 MANE Select	c.277G>A	p.Val93Ile	missense	Exon 1 of 3	ENSP00000290354.5	O75828
CBR3-AS1	ENST00000453159.7	TSL:1	n.271-2395C>T		intron	N/A
CBR3	ENST00000926155.1		c.277G>A	p.Val93Ile	missense	Exon 1 of 2	ENSP00000596214.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

244962

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33342

American (AMR)

AF:

0.0000225

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.00

AC:

AN:

86026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110188

Other (OTH)

AF:

0.00

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000185

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.048

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.76

M_CAP

Benign

0.067

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.75

MutationAssessor

Benign

-0.34

PhyloP100

4.2

PrimateAI

Benign

0.27

PROVEAN

Benign

0.69

REVEL

Benign

0.26

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MutPred

0.21

Gain of methylation at K96 (P = 0.1021)

MVP

0.65

MPC

0.16

ClinPred

0.11

GERP RS

4.0

PromoterAI

0.056

Neutral

(source)

Varity_R

0.19

gMVP

0.16

Mutation Taster

=81/19

polymorphism

(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