rs1327836

Variant names:

• chr9-74677373-T-G
• rs1327836
• NM_006914.4:c.1224+5472T>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.1224+5472T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,124 control chromosomes in the GnomAD database, including 8,337 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 0.29 (8337 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• 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):

• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.1224+5472T>G		intron_variant	Intron 9 of 9	ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.1257+5472T>G		intron_variant	Intron 9 of 9		NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.1224+5472T>G		intron_variant	Intron 9 of 9	1	NM_006914.4	ENSP00000366093.2
RORB	ENST00000396204.2	c.1257+5472T>G		intron_variant	Intron 9 of 9	1		ENSP00000379507.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43539 AN: 152004 Hom.: 8322 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.287 AC: 43596 AN: 152124 Hom.: 8337 Cov.: 32 AF XY: 0.291 AC XY: 21654 AN XY: 74380

African (AFR) AF: 0.503 AC: 20874 AN: 41466

American (AMR) AF: 0.255 AC: 3900 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3493 AN: 5170

South Asian (SAS) AF: 0.204 AC: 983 AN: 4826

European-Finnish (FIN) AF: 0.247 AC: 2618 AN: 10582

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10429 AN: 68014

Other (OTH) AF: 0.253 AC: 532 AN: 2104

Alfa AF: 0.210 Hom.: 8631

Bravo AF: 0.300

Asia WGS AF: 0.410 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.0
DANN	Benign	0.76
PhyloP100		0.49
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: rs1327836; hg19: chr9-77292289; COSMIC: COSV65334409;