rs17691614

Variant names:

• chr9-74630957-A-G
• rs17691614
• NM_006914.4:c.93+590A>G

Variant summary

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

The NM_006914.4(RORB):​c.93+590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,046 control chromosomes in the GnomAD database, including 4,358 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 0.24 (4358 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 6 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

ENSG00000286944 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.93+590A>G		intron_variant	Intron 2 of 9	ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.126+590A>G		intron_variant	Intron 2 of 9		NP_001351952.1
LOC105376088	XR_929948.3	n.*121T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.93+590A>G		intron_variant	Intron 2 of 9	1	NM_006914.4	ENSP00000366093.2
RORB	ENST00000396204.2	c.126+590A>G		intron_variant	Intron 2 of 9	1		ENSP00000379507.2
ENSG00000286944	ENST00000658390.1	n.3420T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36154 AN: 151928 Hom.: 4352 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.238 AC: 36197 AN: 152046 Hom.: 4358 Cov.: 32 AF XY: 0.236 AC XY: 17549 AN XY: 74352

African (AFR) AF: 0.234 AC: 9695 AN: 41474

American (AMR) AF: 0.243 AC: 3717 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3468

East Asian (EAS) AF: 0.163 AC: 844 AN: 5172

South Asian (SAS) AF: 0.305 AC: 1466 AN: 4800

European-Finnish (FIN) AF: 0.199 AC: 2110 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16510 AN: 67954

Other (OTH) AF: 0.249 AC: 526 AN: 2114

Alfa AF: 0.248 Hom.: 5845

Bravo AF: 0.242

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		-0.015
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: rs17691614; hg19: chr9-77245873;