NM_021969.3:c.512G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021969.3(NR0B2):c.512G>C(p.Gly171Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0716 in 1,613,920 control chromosomes in the GnomAD database, including 4,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 375 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4063 hom. )

Consequence

NR0B2
NM_021969.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.90

Publications

43 publications found

Variant links:

Genes affected

NR0B2 (HGNC:7961): (nuclear receptor subfamily 0 group B member 2) The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function. [provided by RefSeq, Jul 2008]

NR0B2 links:

NUDC (HGNC:8045): (nuclear distribution C, dynein complex regulator) This gene encodes a nuclear distribution protein that plays an essential role in mitosis and cytokinesis. The encoded protein is involved in spindle formation during mitosis and in microtubule organization during cytokinesis. Pseudogenes of this gene are found on chromosome 2. [provided by RefSeq, Feb 2012]

NUDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006049454).

BP6

Variant 1-26913429-C-G is Benign according to our data. Variant chr1-26913429-C-G is described in ClinVar as Benign. ClinVar VariationId is 595423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021969.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR0B2	NM_021969.3	MANE Select	c.512G>C	p.Gly171Ala	missense	Exon 1 of 2	NP_068804.1	Q15466

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR0B2	ENST00000254227.4	TSL:1 MANE Select	c.512G>C	p.Gly171Ala	missense	Exon 1 of 2	ENSP00000254227.3	Q15466
	NUDC	ENST00000435827.6	TSL:5	c.93+2194C>G		intron	N/A	ENSP00000404020.2	A0A0A0MSU9

Frequencies

GnomAD3 genomes

AF:

0.0670

AC:

10184

AN:

152008

Hom.:

374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0612

Gnomad AMI

AF:

0.0604

Gnomad AMR

AF:

0.0565

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.0448

Gnomad FIN

AF:

0.0828

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0784

Gnomad OTH

AF:

0.0570

GnomAD2 exomes

AF:

0.0592

AC:

14861

AN:

251016

AF XY:

0.0594

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.0477

Gnomad EAS exome

AF:

0.00359

Gnomad FIN exome

AF:

0.0765

Gnomad NFE exome

AF:

0.0786

Gnomad OTH exome

AF:

0.0600

GnomAD4 exome

AF:

0.0721

AC:

105376

AN:

1461794

Hom.:

4063

Cov.:

AF XY:

0.0711

AC XY:

51683

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0645

AC:

2161

AN:

33480

American (AMR)

AF:

0.0321

AC:

1435

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0505

AC:

1319

AN:

26134

East Asian (EAS)

AF:

0.00202

AC:

AN:

39700

South Asian (SAS)

AF:

0.0430

AC:

3705

AN:

86252

European-Finnish (FIN)

AF:

0.0764

AC:

4083

AN:

53418

Middle Eastern (MID)

AF:

0.0428

AC:

247

AN:

5768

European-Non Finnish (NFE)

AF:

0.0795

AC:

88388

AN:

1111924

Other (OTH)

AF:

0.0655

AC:

3958

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

5000

10000

14999

19999

24999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3200

6400

9600

12800

16000

<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:

0.0670

AC:

10189

AN:

152126

Hom.:

375

Cov.:

AF XY:

0.0663

AC XY:

4932

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0611

AC:

2536

AN:

41502

American (AMR)

AF:

0.0563

AC:

860

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0461

AC:

160

AN:

3470

East Asian (EAS)

AF:

0.00367

AC:

AN:

5172

South Asian (SAS)

AF:

0.0450

AC:

217

AN:

4820

European-Finnish (FIN)

AF:

0.0828

AC:

876

AN:

10586

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0784

AC:

5332

AN:

67992

Other (OTH)

AF:

0.0583

AC:

123

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

481

962

1444

1925

2406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0645

Hom.:

238

Bravo

AF:

0.0647

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0786

AC:

303

ESP6500AA

AF:

0.0617

AC:

272

ESP6500EA

AF:

0.0813

AC:

699

ExAC

AF:

0.0614

AC:

7461

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.90

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.5

PhyloP100

3.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.51

Sift

Uncertain

0.0050

Sift4G

Benign

0.091

Polyphen

0.99

Vest4

0.20

MPC

0.34

ClinPred

0.032

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.67

Mutation Taster

=83/17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over