Variant rs6150 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000378970.5(NR0B1):c.114C>T(p.Cys38=) 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
ENST00000378970.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.978

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 256224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-30309250-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
NR0B1	NM_000475.5 linkuse as main transcript	c.114C>T	p.Cys38=	synonymous_variant	1/2	ENST00000378970.5	NP_000466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR0B1	ENST00000378970.5 linkuse as main transcript	c.114C>T	p.Cys38=	synonymous_variant	1/2	1	NM_000475.5	ENSP00000368253	P1	P51843-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

15982

AN:

111370

Hom.:

1053

Cov.:

AF XY:

0.137

AC XY:

4637

AN XY:

33730

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

GnomAD3 exomes

AF:

0.151

AC:

25469

AN:

168948

Hom.:

1540

AF XY:

0.149

AC XY:

8831

AN XY:

59204

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 SAS exome

AF:

0.0884

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

Gnomad4 AFR exome

AF:

0.0399

Gnomad4 AMR exome

AF:

0.0602

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.0921

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.144

AC:

15990

AN:

111422

Hom.:

1053

Cov.:

AF XY:

0.138

AC XY:

4649

AN XY:

33794

show subpopulations

Gnomad4 AFR

AF:

0.0397

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.0761

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.134

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

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital adrenal hypoplasia, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.6

DANN

Benign

0.80

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