rs7504

Variant names:

• chr1-26911659-A-G
• rs7504
• NM_021969.3:c.*186T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NR0B2	NM_021969.3	c.*186T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000254227.4	NP_068804.1

Ensembl

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

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

African (AFR) AF: 0.624 AC: 9333 AN: 14962

American (AMR) AF: 0.386 AC: 11054 AN: 28656

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 12138 AN: 15774

East Asian (EAS) AF: 0.0580 AC: 1740 AN: 29996

South Asian (SAS) AF: 0.555 AC: 29068 AN: 52406

European-Finnish (FIN) AF: 0.796 AC: 29873 AN: 37524

Middle Eastern (MID) AF: 0.742 AC: 1732 AN: 2334

European-Non Finnish (NFE) AF: 0.795 AC: 253506 AN: 319004

Other (OTH) AF: 0.688 AC: 19539 AN: 28398

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

African (AFR) AF: 0.629 AC: 26091 AN: 41476

American (AMR) AF: 0.506 AC: 7717 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2674 AN: 3472

East Asian (EAS) AF: 0.0608 AC: 314 AN: 5162

South Asian (SAS) AF: 0.521 AC: 2509 AN: 4820

European-Finnish (FIN) AF: 0.801 AC: 8471 AN: 10576

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54122 AN: 67988

Other (OTH) AF: 0.650 AC: 1374 AN: 2114

Alfa AF: 0.741 Hom.: 54381

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
PhyloP100		-0.045
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7504; hg19: chr1-27238150;