rs13293006

chr9-74521980-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006914.4(RORB):c.7+23997C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,548 control chromosomes in the GnomAD database, including 8,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8806 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

Genes affected

RORB (HGNC:10259): (RAR related orphan receptor B) The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It is a DNA-binding protein that can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, and to help regulate the expression of some genes involved in circadian rhythm. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORB	NM_006914.4	c.7+23997C>A		intron_variant		ENST00000376896.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORB	ENST00000376896.8	c.7+23997C>A		intron_variant		1	NM_006914.4	P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 45967 AN: 151430 Hom.: 8808 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.336

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.303 AC: 45961 AN: 151548 Hom.: 8806 Cov.: 32 AF XY: 0.304 AC XY: 22546 AN XY: 74074

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.338

Alfa AF: 0.357 Hom.: 1889

Bravo AF: 0.274

Asia WGS AF: 0.348 AC: 1208 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	7.7
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: rs13293006; hg19: chr9-77136896; COSMIC: COSV65334184;