dbSNP rs41557318: CBR1:p.Pro131Thr (chr21-36071051-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001757.4(CBR1):c.391C>A(p.Pro131Thr) 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. 13/22 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: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CBR1
NM_001757.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.01

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22702876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CBR1	NM_001757.4 link	c.391C>A	p.Pro131Thr	missense_variant	Exon 2 of 3	ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2 link	c.391C>A	p.Pro131Thr	missense_variant	Exon 2 of 3		NP_001273718.1
CBR1-AS1	NR_040084.1 link	n.378-566G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR1	ENST00000290349.11 link	c.391C>A	p.Pro131Thr	missense_variant	Exon 2 of 3	1	NM_001757.4	ENSP00000290349.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723352

African (AFR)

AF:

0.00

AC:

AN:

33292

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.00

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103650

Other (OTH)

AF:

0.00

AC:

AN:

60126

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

.;D;.;T

Eigen

Benign

0.034

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

T;D;D;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;N;.;.

PhyloP100

3.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.6

D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.046

D;T;D;T

Sift4G

Benign

0.13

T;T;D;T

Polyphen

0.0030, 0.47

.;B;P;.

Vest4

0.50

MutPred

0.32

Gain of MoRF binding (P = 0.0606);Gain of MoRF binding (P = 0.0606);Gain of MoRF binding (P = 0.0606);Gain of MoRF binding (P = 0.0606);

MVP

0.37

MPC

0.36

ClinPred

0.91

GERP RS

5.6

Varity_R

0.71

gMVP

0.59

Mutation Taster

=58/42

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