rs13293006

Variant names:

• chr9-74521980-C-A
• rs13293006
• NM_006914.4:c.7+23997C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

RORB Gene-Disease associations (from GenCC):

• epilepsy, idiopathic generalized, susceptibility to, 15

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• epilepsy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006914.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	NM_006914.4	MANE Select	c.7+23997C>A		intron	N/A	NP_008845.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	ENST00000376896.8	TSL:1 MANE Select	c.7+23997C>A		intron	N/A	ENSP00000366093.2

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

African (AFR) AF: 0.0780 AC: 3232 AN: 41460

American (AMR) AF: 0.278 AC: 4216 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1253 AN: 3458

East Asian (EAS) AF: 0.171 AC: 878 AN: 5128

South Asian (SAS) AF: 0.397 AC: 1913 AN: 4818

European-Finnish (FIN) AF: 0.452 AC: 4768 AN: 10540

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28406 AN: 67646

Other (OTH) AF: 0.338 AC: 711 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13293006; hg19: chr9-77136896; COSMIC: COSV65334184;