NM_000475.5:c.114C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000475.5(NR0B1):c.114C>T(p.Cys38Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,205,518 control chromosomes in the GnomAD database, including 14,961 homozygotes. There are 71,232 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1053 hom., 4649 hem., cov: 24)

Exomes 𝑓: 0.19 ( 13908 hom. 66583 hem. )

Consequence

NR0B1
NM_000475.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.978

Publications

11 publications found

Variant links:

Genes affected

NR0B1 (HGNC:7960): (nuclear receptor subfamily 0 group B member 1) This gene encodes a protein that contains a DNA-binding domain. The encoded protein acts as a dominant-negative regulator of transcription which is mediated by the retinoic acid receptor. This protein also functions as an anti-testis gene by acting antagonistically to Sry. Mutations in this gene result in both X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism. [provided by RefSeq, Jul 2008]

NR0B1 Gene-Disease associations (from GenCC):

X-linked adrenal hypoplasia congenita
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
46,XY sex reversal 2
Inheritance: XL Classification: MODERATE Submitted by: Ambry Genetics

NR0B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-30309250-G-A is Benign according to our data. Variant chrX-30309250-G-A is described in ClinVar as Benign. ClinVar VariationId is 256224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.978 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR0B1	NM_000475.5 link	c.114C>T	p.Cys38Cys	synonymous_variant	Exon 1 of 2	ENST00000378970.5	NP_000466.2	P51843-1F1D8P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR0B1	ENST00000378970.5 link	c.114C>T	p.Cys38Cys	synonymous_variant	Exon 1 of 2	1	NM_000475.5	ENSP00000368253.4		P51843-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

15982

AN:

111370

Hom.:

1053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.0754

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.129

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.131

GnomAD2 exomes

AF:

0.151

AC:

25469

AN:

168948

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.0544

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.187

AC:

204878

AN:

1094096

Hom.:

13908

Cov.:

AF XY:

0.185

AC XY:

66583

AN XY:

360502

show subpopulations

African (AFR)

AF:

0.0399

AC:

1051

AN:

26356

American (AMR)

AF:

0.0602

AC:

2106

AN:

34970

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

4300

AN:

19293

East Asian (EAS)

AF:

0.129

AC:

3892

AN:

30090

South Asian (SAS)

AF:

0.0921

AC:

4956

AN:

53830

European-Finnish (FIN)

AF:

0.258

AC:

10121

AN:

39231

Middle Eastern (MID)

AF:

0.132

AC:

545

AN:

4126

European-Non Finnish (NFE)

AF:

0.202

AC:

169823

AN:

840306

Other (OTH)

AF:

0.176

AC:

8084

AN:

45894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

8001

16002

24003

32004

40005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6076

12152

18228

24304

30380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.144

AC:

15990

AN:

111422

Hom.:

1053

Cov.:

AF XY:

0.138

AC XY:

4649

AN XY:

33794

show subpopulations

African (AFR)

AF:

0.0397

AC:

1227

AN:

30872

American (AMR)

AF:

0.102

AC:

1088

AN:

10687

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

577

AN:

2640

East Asian (EAS)

AF:

0.123

AC:

426

AN:

3459

South Asian (SAS)

AF:

0.0761

AC:

204

AN:

2681

European-Finnish (FIN)

AF:

0.248

AC:

1461

AN:

5903

Middle Eastern (MID)

AF:

0.128

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.200

AC:

10560

AN:

52772

Other (OTH)

AF:

0.134

AC:

205

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

451

901

1352

1802

2253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.185

Hom.:

2157

Bravo

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital adrenal hypoplasia, X-linked

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital adrenal hypoplasia, X-linked;C1848296:46,XY sex reversal 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.6

(source)

DANN

Benign

0.80

PhyloP100

0.98

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over