dbSNP rs1143663: CBR1:p.Val88Ile (chr21-36070377-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001757.4(CBR1):c.262G>A(p.Val88Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,609,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CBR1
NM_001757.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Publications

11 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:

ENSG00000289001 (HGNC:):

ENSG00000289001 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: 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=0.29537022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CBR1	NM_001757.4 link	c.262G>A	p.Val88Ile	missense_variant	Exon 1 of 3	ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2 link	c.262G>A	p.Val88Ile	missense_variant	Exon 1 of 3		NP_001273718.1
CBR1-AS1	NR_040084.1 link	n.486C>T		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR1	ENST00000290349.11 link	c.262G>A	p.Val88Ile	missense_variant	Exon 1 of 3	1	NM_001757.4	ENSP00000290349.6

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

242984

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724764

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33372

American (AMR)

AF:

0.00

AC:

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25926

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.00

AC:

AN:

86000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109834

Other (OTH)

AF:

0.00

AC:

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000623

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;.;T

Eigen

Benign

-0.053

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.;.

PhyloP100

3.8

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.39

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.22

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0090, 0.15

.;B;B;.

Vest4

0.18

MVP

0.11

MPC

0.22

ClinPred

0.89

GERP RS

3.9

PromoterAI

0.14

Neutral

(source)

Varity_R

0.17

gMVP

0.45

Mutation Taster

=80/20

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over