Variant 21-36072631-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001757.4(CBR1):c.583G>A(p.Gly195Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0015 in 1,610,824 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 8 hom. )

Consequence

CBR1
NM_001757.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.19

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:):

CBR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016617328).

BP6

Variant 21-36072631-G-A is Benign according to our data. Variant chr21-36072631-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 721199.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBR1	NM_001757.4 linkuse as main transcript	c.583G>A	p.Gly195Arg	missense_variant	3/3	ENST00000290349.11	NP_001748.1	P16152-1A0A384NL53
CBR1	NM_001286789.2 linkuse as main transcript	c.*692G>A		3_prime_UTR_variant	3/3		NP_001273718.1	P16152-2
CBR1-AS1	NR_040084.1 linkuse as main transcript	n.378-2146C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CBR1	ENST00000290349.11 linkuse as main transcript	c.583G>A	p.Gly195Arg	missense_variant	3/3	1	NM_001757.4	ENSP00000290349.6	P16152-1
CBR1	ENST00000530908.5 linkuse as main transcript	c.*692G>A		3_prime_UTR_variant	3/3	1		ENSP00000434613.1	P16152-2
SETD4	ENST00000399201.5 linkuse as main transcript	c.-203+6674C>T		intron_variant		1		ENSP00000382152.1	A8MTS1
CBR1-AS1	ENST00000535199.5 linkuse as main transcript	n.378-2146C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00179

AC:

443

AN:

247836

Hom.:

AF XY:

0.00177

AC XY:

237

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.00154

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00152

AC:

2215

AN:

1458636

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1094

AN XY:

725374

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.000429

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00129

AC:

196

AN:

152188

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00130

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00153

AC:

186

EpiCase

AF:

0.00180

EpiControl

AF:

0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.051

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.24

Sift

Benign

0.067

Sift4G

Benign

0.073

Polyphen

0.99

Vest4

0.75

MutPred

0.53

Gain of MoRF binding (P = 0.0056);

MVP

0.38

MPC

0.62

ClinPred

0.051

GERP RS

5.4

Varity_R

0.87

gMVP

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over