21-36140267-A-G

Variant names:

• chr21-36140267-A-G
• rs10483032
• NM_001236.4:c.397+2335A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001236.4(CBR3):​c.397+2335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 151,938 control chromosomes in the GnomAD database, including 61,316 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61316 hom., cov: 29)
• Consequence: CBR3 NM_001236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3	NM_001236.4	MANE Select	c.397+2335A>G		intron	N/A	NP_001227.1
	CBR3-AS1	NR_038892.1		n.192+5989T>C		intron	N/A
	CBR3-AS1	NR_038893.1		n.192+5989T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3	ENST00000290354.6	TSL:1 MANE Select	c.397+2335A>G		intron	N/A	ENSP00000290354.5
	CBR3-AS1	ENST00000453159.7	TSL:1	n.270+5989T>C		intron	N/A
	CBR3	ENST00000926155.1		c.289+4786A>G		intron	N/A	ENSP00000596214.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136138 AN: 151820 Hom.: 61264 Cov.: 29

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.899

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.897 AC: 136247 AN: 151938 Hom.: 61316 Cov.: 29 AF XY: 0.891 AC XY: 66175 AN XY: 74240

African (AFR) AF: 0.977 AC: 40526 AN: 41496

American (AMR) AF: 0.852 AC: 12986 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3133 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4315 AN: 5094

South Asian (SAS) AF: 0.867 AC: 4178 AN: 4818

European-Finnish (FIN) AF: 0.798 AC: 8430 AN: 10562

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59784 AN: 67928

Other (OTH) AF: 0.895 AC: 1891 AN: 2114

Alfa AF: 0.894 Hom.: 85238

Bravo AF: 0.905

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.032
DANN	Benign	0.47
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs10483032; hg19: chr21-37512565;