rs6150

chrX-30309250-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000475.5(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 NM_000475.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.978

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]

ACMG classification

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	UniProt
NR0B1	NM_000475.5	c.114C>T	p.Cys38=	synonymous_variant	1/2	ENST00000378970.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR0B1	ENST00000378970.5	c.114C>T	p.Cys38=	synonymous_variant	1/2	1	NM_000475.5	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 15982 AN: 111370 Hom.: 1053 Cov.: 24 AF XY: 0.137 AC XY: 4637 AN XY: 33730

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

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.: 35 AF XY: 0.185 AC XY: 66583 AN XY: 360502

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.: 24 AF XY: 0.138 AC XY: 4649 AN XY: 33794

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 07, 2018	- -

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

Invitae

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

Other links and lift over

dbSNP: rs6150; hg19: chrX-30327367; COSMIC: COSV66764107; COSMIC: COSV66764107;