rs8133052

Positions:

• chr21-36135203-G-C
• chr21-36135203-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/21 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. C4Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CBR3 NM_001236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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/exons	MANE	Protein	UniProt
CBR3	NM_001236.4	c.11G>C	p.Cys4Ser	missense_variant	1/3	ENST00000290354.6	NP_001227.1
CBR3	XM_011529772.3	c.11G>C	p.Cys4Ser	missense_variant	1/3		XP_011528074.1
CBR3-AS1	NR_038892.1	n.193-1442C>G		intron_variant
CBR3-AS1	NR_038893.1	n.193-2129C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBR3	ENST00000290354.6	c.11G>C	p.Cys4Ser	missense_variant	1/3	1	NM_001236.4	ENSP00000290354.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1344328 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 657204

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.: 34

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	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.089
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.29		Gain of disorder (P = 0.0034);
MVP		0.38
MPC		0.24
ClinPred		0.064	T
GERP RS		2.5
Varity_R		0.13
gMVP		0.37

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

Other links and lift over

dbSNP: rs8133052; hg19: chr21-37507501;