21-36135298-A-G

Variant names:

• chr21-36135298-A-G
• rs2065649411
• NM_001236.4:c.106A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001236.4(CBR3):​c.106A>G​(p.Thr36Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T36P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CBR3 NM_001236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36344784).

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.106A>G	p.Thr36Ala	missense	Exon 1 of 3	NP_001227.1	O75828
	CBR3-AS1	NR_038892.1		n.193-1537T>C		intron	N/A
	CBR3-AS1	NR_038893.1		n.193-2224T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3	ENST00000290354.6	TSL:1 MANE Select	c.106A>G	p.Thr36Ala	missense	Exon 1 of 3	ENSP00000290354.5	O75828
	CBR3-AS1	ENST00000453159.7	TSL:1	n.271-2224T>C		intron	N/A
	CBR3	ENST00000926155.1		c.106A>G	p.Thr36Ala	missense	Exon 1 of 2	ENSP00000596214.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.030	D
MutationAssessor	Benign	1.3	L
PhyloP100		4.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.040	D
Polyphen		0.45	B
Vest4		0.22
MutPred		0.63		Loss of phosphorylation at T36 (P = 0.048)
MVP		0.84
MPC		0.22
ClinPred		0.98	D
GERP RS		4.1
PromoterAI		0.11	Neutral
Varity_R		0.65
gMVP		0.67
Mutation Taster		=51/49	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: rs2065649411; hg19: chr21-37507596;