Variant chr21-36146292-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001236.4(CBR3):c.614C>G(p.Ser205Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

CBR3
NM_001236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CBR3	NM_001236.4 linkuse as main transcript	c.614C>G	p.Ser205Trp	missense_variant	3/3	ENST00000290354.6	NP_001227.1
CBR3-AS1	NR_038893.1 linkuse as main transcript	n.156G>C		non_coding_transcript_exon_variant	2/3
CBR3-AS1	NR_038892.1 linkuse as main transcript	n.156G>C		non_coding_transcript_exon_variant	2/4
CBR3-AS1	NR_038894.1 linkuse as main transcript	n.156G>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBR3	ENST00000290354.6 linkuse as main transcript	c.614C>G	p.Ser205Trp	missense_variant	3/3	1	NM_001236.4	ENSP00000290354	P1
CBR3-AS1	ENST00000624080.1 linkuse as main transcript	n.149-12819G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152116

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251418

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.614C>G (p.S205W) alteration is located in exon 3 (coding exon 3) of the CBR3 gene. This alteration results from a C to G substitution at nucleotide position 614, causing the serine (S) at amino acid position 205 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.77

MVP

0.69

MPC

0.90

ClinPred

0.97

GERP RS

4.8

Varity_R

0.89

gMVP

0.82

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over