X-30304336-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000475.5(NR0B1):c.*242del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 302,578 control chromosomes in the GnomAD database, including 47 homozygotes. There are 591 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (39 hom., 455 hem., cov: 22)
  • Exomes 𝑓: 0.0089 (8 hom. 136 hem.)
• Consequence: NR0B1 NM_000475.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.786

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 -10 ACMG points.

• BP6: Variant X-30304336-AT-A is Benign according to our data. Variant chrX-30304336-AT-A is described in ClinVar as [Benign]. Clinvar id is 1278137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR0B1	NM_000475.5	c.*242del		3_prime_UTR_variant	2/2	ENST00000378970.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR0B1	ENST00000378970.5	c.*242del		3_prime_UTR_variant	2/2	1	NM_000475.5	P1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 1899 AN: 108344 Hom.: 39 Cov.: 22 AF XY: 0.0145 AC XY: 457 AN XY: 31570

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00769

Gnomad ASJ AF: 0.000387

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000393

Gnomad FIN AF: 0.000556

Gnomad MID AF: 0.0297

Gnomad NFE AF: 0.000577

Gnomad OTH AF: 0.00898

GnomAD4 exome AF: 0.00888 AC: 1724 AN: 194198 Hom.: 8 Cov.: 3 AF XY: 0.00251 AC XY: 136 AN XY: 54250

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00676

Gnomad4 EAS exome AF: 0.00547

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00666

Gnomad4 NFE exome AF: 0.00627

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0175 AC: 1898 AN: 108380 Hom.: 39 Cov.: 22 AF XY: 0.0144 AC XY: 455 AN XY: 31616

Gnomad4 AFR AF: 0.0591

Gnomad4 AMR AF: 0.00768

Gnomad4 ASJ AF: 0.000387

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000395

Gnomad4 FIN AF: 0.000556

Gnomad4 NFE AF: 0.000577

Gnomad4 OTH AF: 0.00886

Bravo AF: 0.0206

Asia WGS AF: 0.00399 AC: 10 AN: 2516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs373100951; hg19: chrX-30322453;