NM_006914.4:c.7+36938A>G

Variant names:

• chr9-74534921-A-G
• rs7042950
• NM_006914.4:c.7+36938A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006914.4(RORB):​c.7+36938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,986 control chromosomes in the GnomAD database, including 6,419 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 0.27 (6419 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 27 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
• epilepsy, idiopathic generalized, susceptibility to, 15

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	NM_006914.4	MANE Select	c.7+36938A>G		intron	N/A	NP_008845.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	ENST00000376896.8	TSL:1 MANE Select	c.7+36938A>G		intron	N/A	ENSP00000366093.2	Q92753-1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41552 AN: 151868 Hom.: 6427 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.273 AC: 41567 AN: 151986 Hom.: 6419 Cov.: 32 AF XY: 0.277 AC XY: 20608 AN XY: 74292

African (AFR) AF: 0.303 AC: 12566 AN: 41466

American (AMR) AF: 0.272 AC: 4152 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1167 AN: 3464

East Asian (EAS) AF: 0.756 AC: 3884 AN: 5140

South Asian (SAS) AF: 0.370 AC: 1786 AN: 4822

European-Finnish (FIN) AF: 0.213 AC: 2255 AN: 10594

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15055 AN: 67936

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.245 Hom.: 20431

Bravo AF: 0.284

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		1.0
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: rs7042950; hg19: chr9-77149837;