NM_021969.3:c.*101C>G

Variant names:

• chr1-26911744-G-C
• rs41303639
• NM_021969.3:c.*101C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 6 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR0B2	NM_021969.3	MANE Select	c.*101C>G		3_prime_UTR	Exon 2 of 2	NP_068804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR0B2	ENST00000254227.4	TSL:1 MANE Select	c.*101C>G		3_prime_UTR	Exon 2 of 2	ENSP00000254227.3
	NUDC	ENST00000435827.6	TSL:5	c.93+509G>C		intron	N/A	ENSP00000404020.2

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9662 AN: 152110 Hom.: 319 Cov.: 32

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.: 17 AF XY: 0.0677 AC XY: 42905 AN XY: 633322

African (AFR) AF: 0.0617 AC: 1819 AN: 29464

American (AMR) AF: 0.0297 AC: 1201 AN: 40404

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 1092 AN: 24620

East Asian (EAS) AF: 0.0118 AC: 449 AN: 38090

South Asian (SAS) AF: 0.0603 AC: 4849 AN: 80450

European-Finnish (FIN) AF: 0.0580 AC: 3000 AN: 51728

Middle Eastern (MID) AF: 0.0630 AC: 340 AN: 5394

European-Non Finnish (NFE) AF: 0.0739 AC: 68887 AN: 932734

Other (OTH) AF: 0.0642 AC: 3434 AN: 53522

GnomAD4 genome AF: 0.0637 AC: 9697 AN: 152228 Hom.: 325 Cov.: 32 AF XY: 0.0614 AC XY: 4566 AN XY: 74422

African (AFR) AF: 0.0653 AC: 2714 AN: 41546

American (AMR) AF: 0.0440 AC: 672 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3472

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5176

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4822

European-Finnish (FIN) AF: 0.0557 AC: 591 AN: 10604

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5007 AN: 68006

Other (OTH) AF: 0.0626 AC: 132 AN: 2108

Alfa AF: 0.0290 Hom.: 17

Bravo AF: 0.0620

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.2
DANN	Benign	0.85
PhyloP100		-0.33
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: rs41303639; hg19: chr1-27238235; COSMIC: COSV54259558;