rs780228078

Variant names:

• chr21-36146309-C-A
• NM_001236.4:c.631C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-36146309-C-A
• chr21-36146309-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001236.4(CBR3):​c.631C>A​(p.Arg211Ser) 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. 15/21 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. R211C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBR3 NM_001236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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

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=0.08738056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBR3	NM_001236.4	c.631C>A	p.Arg211Ser	missense_variant	Exon 3 of 3	ENST00000290354.6	NP_001227.1
CBR3-AS1	NR_038892.1	n.139G>T		non_coding_transcript_exon_variant	Exon 2 of 4
CBR3-AS1	NR_038893.1	n.139G>T		non_coding_transcript_exon_variant	Exon 2 of 3
CBR3-AS1	NR_038894.1	n.139G>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR3	ENST00000290354.6	c.631C>A	p.Arg211Ser	missense_variant	Exon 3 of 3	1	NM_001236.4	ENSP00000290354.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.033
Sift	Benign	0.41	T
Sift4G	Benign	0.38	T
Polyphen		0.015	B
Vest4		0.12
MutPred		0.49		Gain of phosphorylation at R211 (P = 0.028);
MVP		0.43
MPC		0.22
ClinPred		0.073	T
GERP RS		2.7
Varity_R		0.27
gMVP		0.62

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.

Other links and lift over

hg19: chr21-37518607;