rs10217594

Variant names:

• chr9-74544349-C-T
• rs10217594
• NM_006914.4:c.7+46366C>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.7+46366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,068 control chromosomes in the GnomAD database, including 5,854 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 (5854 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• 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):

• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 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+46366C>T		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+46366C>T		intron	N/A	ENSP00000366093.2	Q92753-1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41340 AN: 151950 Hom.: 5847 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.272 AC: 41367 AN: 152068 Hom.: 5854 Cov.: 32 AF XY: 0.269 AC XY: 19983 AN XY: 74326

African (AFR) AF: 0.277 AC: 11481 AN: 41472

American (AMR) AF: 0.370 AC: 5656 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3472

East Asian (EAS) AF: 0.0788 AC: 408 AN: 5178

South Asian (SAS) AF: 0.202 AC: 974 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10568

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18892 AN: 67982

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.279 Hom.: 7875

Bravo AF: 0.287

Asia WGS AF: 0.161 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		-0.063
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: rs10217594; hg19: chr9-77159265;