rs7022435

Variant names:

• chr9-74629537-G-A
• rs7022435
• NM_006914.4:c.8-745G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-74629537-G-A
• chr9-74629537-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.8-745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,326 control chromosomes in the GnomAD database, including 3,266 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 0.21 (3266 hom., cov: 29)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-745G>A		intron_variant	Intron 1 of 9	ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.41-745G>A		intron_variant	Intron 1 of 9		NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.8-745G>A		intron_variant	Intron 1 of 9	1	NM_006914.4	ENSP00000366093.2
RORB	ENST00000396204.2	c.41-745G>A		intron_variant	Intron 1 of 9	1		ENSP00000379507.2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31211 AN: 151210 Hom.: 3261 Cov.: 29

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.206 AC: 31240 AN: 151326 Hom.: 3266 Cov.: 29 AF XY: 0.206 AC XY: 15218 AN XY: 73856

African (AFR) AF: 0.187 AC: 7716 AN: 41218

American (AMR) AF: 0.183 AC: 2772 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3466

East Asian (EAS) AF: 0.0587 AC: 299 AN: 5096

South Asian (SAS) AF: 0.193 AC: 919 AN: 4774

European-Finnish (FIN) AF: 0.219 AC: 2290 AN: 10450

Middle Eastern (MID) AF: 0.189 AC: 54 AN: 286

European-Non Finnish (NFE) AF: 0.237 AC: 16062 AN: 67844

Other (OTH) AF: 0.204 AC: 428 AN: 2096

Alfa AF: 0.212 Hom.: 2137

Bravo AF: 0.199

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.97
DANN	Benign	0.55
PhyloP100		-0.38
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: rs7022435; hg19: chr9-77244453;