1-26913429-C-G

Position:

chr1-26913429-C-G

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR0B2	NM_021969.3 linkuse as main transcript	c.512G>C	p.Gly171Ala	missense_variant	1/2	ENST00000254227.4	NP_068804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR0B2	ENST00000254227.4 linkuse as main transcript	c.512G>C	p.Gly171Ala	missense_variant	1/2	1	NM_021969.3	ENSP00000254227	P1
NUDC	ENST00000435827.6 linkuse as main transcript	c.93+2194C>G		intron_variant		5		ENSP00000404020

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

GnomAD3 exomes

AF:

0.0592

AC:

14861

AN:

251016

Hom.:

520

AF XY:

0.0594

AC XY:

8059

AN XY:

135686

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 SAS exome

AF:

0.0435

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

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.0321

Gnomad4 ASJ exome

AF:

0.0505

Gnomad4 EAS exome

AF:

0.00202

Gnomad4 SAS exome

AF:

0.0430

Gnomad4 FIN exome

AF:

0.0764

Gnomad4 NFE exome

AF:

0.0795

Gnomad4 OTH exome

AF:

0.0655

GnomAD4 genome

AF:

0.0670

AC:

10189

AN:

152126

Hom.:

375

Cov.:

AF XY:

0.0663

AC XY:

4932

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0611

Gnomad4 AMR

AF:

0.0563

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.0450

Gnomad4 FIN

AF:

0.0828

Gnomad4 NFE

AF:

0.0784

Gnomad4 OTH

AF:

0.0583

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 19, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.16

CADD

Benign

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

MutationTaster

Benign

1.0

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

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