rs17612778

Variant names:

• chr9-74603758-C-A
• rs17612778
• NM_006914.4:c.8-26524C>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.8-26524C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,090 control chromosomes in the GnomAD database, including 7,507 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 0.31 (7507 hom., cov: 33)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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.8-26524C>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.8-26524C>A		intron	N/A	ENSP00000366093.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47194 AN: 151970 Hom.: 7501 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.311 AC: 47228 AN: 152090 Hom.: 7507 Cov.: 33 AF XY: 0.307 AC XY: 22840 AN XY: 74342

African (AFR) AF: 0.259 AC: 10725 AN: 41482

American (AMR) AF: 0.317 AC: 4840 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3464

East Asian (EAS) AF: 0.151 AC: 782 AN: 5174

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3181 AN: 10576

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23583 AN: 67982

Other (OTH) AF: 0.331 AC: 698 AN: 2106

Alfa AF: 0.321 Hom.: 1167

Bravo AF: 0.310

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.25
PhyloP100		-0.36
Mutation Taster		=99/1	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: rs17612778; hg19: chr9-77218674;