NM_001236.4:c.11G>C

Variant names:

• chr21-36135203-G-C
• rs8133052
• NM_001236.4:c.11G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 77 publications found

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:43664): (CBR3 antisense RNA 1)

ACMG classification

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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3	NM_001236.4	MANE Select	c.11G>C	p.Cys4Ser	missense	Exon 1 of 3	NP_001227.1	O75828
	CBR3-AS1	NR_038892.1		n.193-1442C>G		intron	N/A
	CBR3-AS1	NR_038893.1		n.193-2129C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3	ENST00000290354.6	TSL:1 MANE Select	c.11G>C	p.Cys4Ser	missense	Exon 1 of 3	ENSP00000290354.5	O75828
	CBR3-AS1	ENST00000453159.7	TSL:1	n.271-2129C>G		intron	N/A
	CBR3	ENST00000926155.1		c.11G>C	p.Cys4Ser	missense	Exon 1 of 2	ENSP00000596214.1

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

African (AFR) AF: 0.00 AC: 0 AN: 29692

American (AMR) AF: 0.00 AC: 0 AN: 29652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20916

East Asian (EAS) AF: 0.00 AC: 0 AN: 35348

South Asian (SAS) AF: 0.00 AC: 0 AN: 69820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055288

Other (OTH) AF: 0.00 AC: 0 AN: 55726

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 42651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.16
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
PromoterAI		0.074	Neutral
Varity_R		0.13
gMVP		0.37
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs8133052; hg19: chr21-37507501;