rs132630327

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2

The NM_000475.5(NR0B1):c.315G>C(p.Trp105Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,207,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000028 ( 0 hom. 11 hem. )

Consequence

NR0B1
NM_000475.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 4.21

Publications

10 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: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.864

BP6

Variant X-30309049-C-G is Benign according to our data. Variant chrX-30309049-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 10978.

BS2

High Hemizygotes in GnomAdExome4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR0B1	NM_000475.5 link	c.315G>C	p.Trp105Cys	missense_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.315G>C	p.Trp105Cys	missense_variant	Exon 1 of 2	1	NM_000475.5	ENSP00000368253.4		P51843-1

Frequencies

GnomAD3 genomes

AF:

0.0000449

AC:

AN:

111243

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000945

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

178455

AF XY:

0.0000456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000636

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1095958

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

362474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26359

American (AMR)

AF:

0.00

AC:

AN:

34431

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19323

East Asian (EAS)

AF:

0.00

AC:

AN:

29996

South Asian (SAS)

AF:

0.00

AC:

AN:

53952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40003

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.0000368

AC:

AN:

841771

Other (OTH)

AF:

0.00

AC:

AN:

45990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000449

AC:

AN:

111243

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33597

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30489

American (AMR)

AF:

0.00

AC:

AN:

10665

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2631

East Asian (EAS)

AF:

0.00

AC:

AN:

3485

South Asian (SAS)

AF:

0.00

AC:

AN:

2600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0000945

AC:

AN:

52891

Other (OTH)

AF:

0.00

AC:

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000868

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

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

Uncertain:1Benign:1

Jun 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 02, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mineralocorticoid deficiency, isolated

Uncertain:1

Mar 01, 2007

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.92

MetaRNN

Pathogenic

0.86

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.6

PhyloP100

4.2

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.6

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.57

MutPred

0.69

Gain of disorder (P = 0.0024);

MVP

0.98

MPC

1.9

ClinPred

0.47

GERP RS

4.4

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.86

gMVP

0.87

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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