Variant 1-26911744-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021969.3(NR0B2):c.*101C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,408,634 control chromosomes in the GnomAD database, including 3,410 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.064 ( 325 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3085 hom. )

Consequence

NR0B2
NM_021969.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.326

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR0B2	NM_021969.3 link	c.*101C>G		3_prime_UTR_variant	2/2	ENST00000254227.4	NP_068804.1	Q15466

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR0B2	ENST00000254227 link	c.*101C>G		3_prime_UTR_variant	2/2	1	NM_021969.3	ENSP00000254227.3		Q15466
NUDC	ENST00000435827.6 link	c.93+509G>C		intron_variant		5		ENSP00000404020.2		A0A0A0MSU9

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9662

AN:

152110

Hom.:

319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0441

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0177

Gnomad SAS

AF:

0.0593

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.0628

GnomAD4 exome

AF:

0.0677

AC:

85071

AN:

1256406

Hom.:

3085

Cov.:

AF XY:

0.0677

AC XY:

42905

AN XY:

633322

show subpopulations

Gnomad4 AFR exome

AF:

0.0617

Gnomad4 AMR exome

AF:

0.0297

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.0118

Gnomad4 SAS exome

AF:

0.0603

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0739

Gnomad4 OTH exome

AF:

0.0642

GnomAD4 genome

AF:

0.0637

AC:

9697

AN:

152228

Hom.:

325

Cov.:

AF XY:

0.0614

AC XY:

4566

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0653

Gnomad4 AMR

AF:

0.0440

Gnomad4 ASJ

AF:

0.0429

Gnomad4 EAS

AF:

0.0178

Gnomad4 SAS

AF:

0.0591

Gnomad4 FIN

AF:

0.0557

Gnomad4 NFE

AF:

0.0736

Gnomad4 OTH

AF:

0.0626

Alfa

AF:

0.0290

Hom.:

Bravo

AF:

0.0620

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.2

DANN

Benign

0.85

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over