Variant X-30308866-C-T 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 NM_000475.5(NR0B1):c.498G>A(p.Arg166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,204,414 control chromosomes in the GnomAD database, including 30,177 homozygotes. There are 100,218 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 4242 hom., 9254 hem., cov: 23)

Exomes 𝑓: 0.24 ( 25935 hom. 90964 hem. )

Consequence

NR0B1
NM_000475.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.477

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=-0.8).

BP6

Variant X-30308866-C-T is Benign according to our data. Variant chrX-30308866-C-T is described in ClinVar as [Benign]. Clinvar id is 256225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-30308866-C-T is described in Lovd as [Pathogenic]. Variant chrX-30308866-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.477 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 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.498G>A	p.Arg166=	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.498G>A	p.Arg166=	synonymous_variant	1/2	1	NM_000475.5	ENSP00000368253	P1	P51843-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

32511

AN:

109841

Hom.:

4241

Cov.:

AF XY:

0.285

AC XY:

9220

AN XY:

32299

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.0775

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.334

AC:

56300

AN:

168478

Hom.:

7800

AF XY:

0.330

AC XY:

19196

AN XY:

58244

show subpopulations

Gnomad AFR exome

AF:

0.452

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.725

Gnomad SAS exome

AF:

0.522

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.244

AC:

266596

AN:

1094516

Hom.:

25935

Cov.:

AF XY:

0.252

AC XY:

90964

AN XY:

360844

show subpopulations

Gnomad4 AFR exome

AF:

0.437

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.670

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.296

AC:

32552

AN:

109898

Hom.:

4242

Cov.:

AF XY:

0.286

AC XY:

9254

AN XY:

32366

show subpopulations

Gnomad4 AFR

AF:

0.429

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.550

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.251

Hom.:

2773

Bravo

AF:

0.326

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 01, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

-0.80

CADD

Benign

6.0

DANN

Benign

0.90

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