chr21-36135361-C-T

Variant names:

• chr21-36135361-C-T
• NM_001236.4:c.169C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001236.4(CBR3):​c.169C>T​(p.Pro57Ser) 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: 34)
• Consequence: CBR3 NM_001236.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.169C>T	p.Pro57Ser	missense	Exon 1 of 3	NP_001227.1	O75828
	CBR3-AS1	NR_038892.1		n.193-1600G>A		intron	N/A
	CBR3-AS1	NR_038893.1		n.193-2287G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3	ENST00000290354.6	TSL:1 MANE Select	c.169C>T	p.Pro57Ser	missense	Exon 1 of 3	ENSP00000290354.5	O75828
	CBR3-AS1	ENST00000453159.7	TSL:1	n.271-2287G>A		intron	N/A
	CBR3	ENST00000926155.1		c.169C>T	p.Pro57Ser	missense	Exon 1 of 2	ENSP00000596214.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.022	D
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.63		Loss of sheet (P = 0.0817)
MVP		0.89
MPC		0.64
ClinPred		0.98	D
GERP RS		5.3
PromoterAI		0.037	Neutral
Varity_R		0.84
gMVP		0.61
Mutation Taster		=85/15	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

hg19: chr21-37507659;