dbSNP rs9024: CBR1:c.*133G>A (chr21-36073015-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001757.4(CBR1):c.*133G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 597,352 control chromosomes in the GnomAD database, including 5,455 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 0.10 ( 1027 hom., cov: 32)

Exomes 𝑓: 0.13 ( 4428 hom. )

Consequence

CBR1
NM_001757.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

54 publications found

Variant links:

Genes affected

CBR1 (HGNC:1548): (carbonyl reductase 1) The protein encoded by this gene belongs to the short-chain dehydrogenases/reductases (SDR) family, which function as NADPH-dependent oxidoreductases having wide specificity for carbonyl compounds, such as quinones, prostaglandins, and various xenobiotics. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

CBR1 links:

SETD4 (HGNC:1258): (SET domain containing 4) Enables histone methyltransferase activity (H4-K20 specific). Involved in histone H4-K20 trimethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SETD4 links:

CBR1-AS1 (HGNC:55777): (CBR1 antisense RNA 1)

CBR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CBR1	NM_001757.4 link	c.*133G>A	3_prime_UTR_variant	Exon 3 of 3	ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2 link	c.*1076G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001273718.1
CBR1-AS1	NR_040084.1 link	n.377+1866C>T	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CBR1	ENST00000290349.11 link	c.*133G>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_001757.4	ENSP00000290349.6
CBR1	ENST00000530908.5 link	c.*1076G>A	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000434613.1
SETD4	ENST00000399201.5 link	c.-203+6290C>T	intron_variant	Intron 1 of 7	1		ENSP00000382152.1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15389

AN:

152122

Hom.:

1025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0958

GnomAD4 exome

AF:

0.133

AC:

59205

AN:

445112

Hom.:

4428

Cov.:

AF XY:

0.135

AC XY:

31219

AN XY:

230844

show subpopulations

African (AFR)

AF:

0.0243

AC:

296

AN:

12170

American (AMR)

AF:

0.179

AC:

2713

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

942

AN:

12918

East Asian (EAS)

AF:

0.254

AC:

7520

AN:

29610

South Asian (SAS)

AF:

0.196

AC:

6730

AN:

34256

European-Finnish (FIN)

AF:

0.129

AC:

3564

AN:

27710

Middle Eastern (MID)

AF:

0.0765

AC:

147

AN:

1922

European-Non Finnish (NFE)

AF:

0.120

AC:

34241

AN:

286046

Other (OTH)

AF:

0.120

AC:

3052

AN:

25352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2479

4958

7437

9916

12395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15396

AN:

152240

Hom.:

1027

Cov.:

AF XY:

0.102

AC XY:

7599

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0245

AC:

1016

AN:

41546

American (AMR)

AF:

0.143

AC:

2194

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0643

AC:

223

AN:

3468

East Asian (EAS)

AF:

0.216

AC:

1117

AN:

5180

South Asian (SAS)

AF:

0.179

AC:

864

AN:

4828

European-Finnish (FIN)

AF:

0.132

AC:

1398

AN:

10598

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8333

AN:

68004

Other (OTH)

AF:

0.0976

AC:

206

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

679

1358

2037

2716

3395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.116

Hom.:

4860

Bravo

AF:

0.0961

Asia WGS

AF:

0.229

AC:

794

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.053

(source)

DANN

Benign

0.61

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over