rs10869430

Variant names:

• chr9-74621347-G-A
• rs10869430
• NM_006914.4:c.8-8935G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-74621347-G-A
• chr9-74621347-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006914.4(RORB):​c.8-8935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,924 control chromosomes in the GnomAD database, including 8,343 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 0.32 (8343 hom., cov: 33)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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.8-8935G>A		intron	N/A	NP_008845.2
	RORB	NM_001365023.1		c.40+5708G>A		intron	N/A	NP_001351952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	ENST00000376896.8	TSL:1 MANE Select	c.8-8935G>A		intron	N/A	ENSP00000366093.2
	RORB	ENST00000396204.2	TSL:1	c.40+5708G>A		intron	N/A	ENSP00000379507.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48610 AN: 151806 Hom.: 8349 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.320 AC: 48605 AN: 151924 Hom.: 8343 Cov.: 33 AF XY: 0.324 AC XY: 24048 AN XY: 74232

African (AFR) AF: 0.204 AC: 8469 AN: 41436

American (AMR) AF: 0.337 AC: 5150 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2979 AN: 5162

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4812

European-Finnish (FIN) AF: 0.404 AC: 4252 AN: 10512

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23779 AN: 67946

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.341 Hom.: 15464

Bravo AF: 0.312

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-0.068
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: rs10869430; hg19: chr9-77236263;