Variant chr21-36135197-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001236.4(CBR3):c.5C>G(p.Ser2Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CBR3
NM_001236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue N-acetylserine (size 0) in uniprot entity CBR3_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CBR3	NM_001236.4 linkuse as main transcript	c.5C>G	p.Ser2Trp	missense_variant	1/3	ENST00000290354.6	NP_001227.1
CBR3-AS1	NR_038893.1 linkuse as main transcript	n.193-2123G>C		intron_variant, non_coding_transcript_variant
CBR3	XM_011529772.3 linkuse as main transcript	c.5C>G	p.Ser2Trp	missense_variant	1/3		XP_011528074.1
CBR3-AS1	NR_038892.1 linkuse as main transcript	n.193-1436G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBR3	ENST00000290354.6 linkuse as main transcript	c.5C>G	p.Ser2Trp	missense_variant	1/3	1	NM_001236.4	ENSP00000290354	P1
CBR3-AS1	ENST00000624080.1 linkuse as main transcript	n.149-1724G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1329200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648606

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 21, 2023

The c.5C>G (p.S2W) alteration is located in exon 1 (coding exon 1) of the CBR3 gene. This alteration results from a C to G substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 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

Benign

0.21

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.077

MetaRNN

Uncertain

0.63

MetaSVM

Uncertain

-0.060

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.42

MutPred

0.41

Loss of disorder (P = 0.0028);

MVP

0.90

MPC

0.73

ClinPred

0.98

GERP RS

5.7

Varity_R

0.19

gMVP

0.66

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over