rs7504

Positions:

• chr1-26911659-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021969.3(NR0B2):​c.*186T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 681,134 control chromosomes in the GnomAD database, including 176,757 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 0.69 (37801 hom., cov: 32)
  • Exomes 𝑓: 0.70 (138956 hom.)
• Consequence: NR0B2 NM_021969.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR0B2	NM_021969.3	c.*186T>C		3_prime_UTR_variant	2/2	ENST00000254227.4	NP_068804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR0B2	ENST00000254227.4	c.*186T>C		3_prime_UTR_variant	2/2	1	NM_021969.3	ENSP00000254227	P1
NUDC	ENST00000435827.6	c.93+424A>G		intron_variant		5		ENSP00000404020

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104083 AN: 151962 Hom.: 37763 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.0607

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.696 AC: 367983 AN: 529054 Hom.: 138956 Cov.: 6 AF XY: 0.693 AC XY: 192567 AN XY: 278074

Gnomad4 AFR exome AF: 0.624

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.0580

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.685 AC: 104176 AN: 152080 Hom.: 37801 Cov.: 32 AF XY: 0.675 AC XY: 50176 AN XY: 74330

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.650

Alfa AF: 0.750 Hom.: 42123

Bravo AF: 0.658

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.2
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs7504; hg19: chr1-27238150;