Genetic Variant CBR3:p.Cys4Ser (chr21-36135203-G-C) – 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.11G>C(p.Cys4Ser) variant causes a missense 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. 17/22 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: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CBR3
NM_001236.4 missense

Scores

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 links:

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

CBR3-AS1 links:

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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=0.16526872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CBR3	NM_001236.4 link	c.11G>C	p.Cys4Ser	missense_variant	Exon 1 of 3	ENST00000290354.6	NP_001227.1
CBR3	XM_011529772.3 link	c.11G>C	p.Cys4Ser	missense_variant	Exon 1 of 3		XP_011528074.1
CBR3-AS1	NR_038892.1 link	n.193-1442C>G		intron_variant	Intron 2 of 3
CBR3-AS1	NR_038893.1 link	n.193-2129C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR3	ENST00000290354.6 link	c.11G>C	p.Cys4Ser	missense_variant	Exon 1 of 3	1	NM_001236.4	ENSP00000290354.5		O75828

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1344328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

657204

African (AFR)

AF:

0.00

AC:

AN:

29692

American (AMR)

AF:

0.00

AC:

AN:

29652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20916

East Asian (EAS)

AF:

0.00

AC:

AN:

35348

South Asian (SAS)

AF:

0.00

AC:

AN:

69820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1055288

Other (OTH)

AF:

0.00

AC:

AN:

55726

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

42651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0092

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.29

M_CAP

Benign

0.0043

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

PhyloP100

0.16

PrimateAI

Benign

0.31

PROVEAN

Benign

0.25

REVEL

Benign

0.089

Sift

Benign

1.0

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.14

MutPred

0.29

Gain of disorder (P = 0.0034);

MVP

0.38

MPC

0.24

ClinPred

0.064

GERP RS

2.5

PromoterAI

0.074

Neutral

(source)

Varity_R

0.13

gMVP

0.37

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over