1-26911960-G-A

Position:

chr1-26911960-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000254227.4(NR0B2):c.659C>T(p.Thr220Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,614,240 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 11 hom. )

Consequence

NR0B2
ENST00000254227.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068087876).

BP6

Variant 1-26911960-G-A is Benign according to our data. Variant chr1-26911960-G-A is described in ClinVar as [Benign]. Clinvar id is 2192638.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR0B2	NM_021969.3 linkuse as main transcript	c.659C>T	p.Thr220Met	missense_variant	2/2	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.659C>T	p.Thr220Met	missense_variant	2/2	1	NM_021969.3	ENSP00000254227	P1
NUDC	ENST00000435827.6 linkuse as main transcript	c.93+725G>A		intron_variant		5		ENSP00000404020

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

188

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00156

AC:

393

AN:

251476

Hom.:

AF XY:

0.00160

AC XY:

218

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.000652

AC:

953

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

492

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.00123

AC:

188

AN:

152354

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00128

AC:

156

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.1

DANN

Benign

0.94

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0068

MetaSVM

Uncertain

-0.063

MutationAssessor

Benign

-0.47

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.88

REVEL

Benign

0.21

Sift

Benign

0.17

Sift4G

Benign

0.14

Polyphen

0.077

Vest4

0.061

MVP

0.33

MPC

0.060

ClinPred

0.020

GERP RS

-0.85

Varity_R

0.021

gMVP

0.39

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