rs17612874

Variant names:

• chr9-74604361-C-A
• rs17612874
• NM_006914.4:c.8-25921C>A

Variant summary

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

The NM_006914.4(RORB):​c.8-25921C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 152,264 control chromosomes in the GnomAD database, including 589 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 0.078 (589 hom., cov: 33)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-25921C>A		intron_variant	Intron 1 of 9	ENST00000376896.8	NP_008845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.8-25921C>A		intron_variant	Intron 1 of 9	1	NM_006914.4	ENSP00000366093.2

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 11866 AN: 152146 Hom.: 589 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.0779 AC: 11855 AN: 152264 Hom.: 589 Cov.: 33 AF XY: 0.0756 AC XY: 5630 AN XY: 74446

African (AFR) AF: 0.0202 AC: 838 AN: 41554

American (AMR) AF: 0.0814 AC: 1245 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 439 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4828

European-Finnish (FIN) AF: 0.100 AC: 1065 AN: 10600

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7733 AN: 68008

Other (OTH) AF: 0.0803 AC: 170 AN: 2116

Alfa AF: 0.0888 Hom.: 112

Bravo AF: 0.0755

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		0.29
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: rs17612874; hg19: chr9-77219277;