rs11144047

Variant names:

• chr9-74661489-C-T
• rs11144047
• NM_006914.4:c.759+751C>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.759+751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 151,964 control chromosomes in the GnomAD database, including 560 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 0.069 (560 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.759+751C>T		intron_variant	Intron 5 of 9	ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.792+751C>T		intron_variant	Intron 5 of 9		NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.759+751C>T		intron_variant	Intron 5 of 9	1	NM_006914.4	ENSP00000366093.2
RORB	ENST00000396204.2	c.792+751C>T		intron_variant	Intron 5 of 9	1		ENSP00000379507.2

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10539 AN: 151846 Hom.: 561 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0694 AC: 10542 AN: 151964 Hom.: 560 Cov.: 32 AF XY: 0.0726 AC XY: 5395 AN XY: 74270

African (AFR) AF: 0.0296 AC: 1226 AN: 41448

American (AMR) AF: 0.0607 AC: 926 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.308 AC: 1593 AN: 5168

South Asian (SAS) AF: 0.0772 AC: 372 AN: 4818

European-Finnish (FIN) AF: 0.0991 AC: 1042 AN: 10512

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0716 AC: 4866 AN: 67968

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0702 Hom.: 160

Bravo AF: 0.0650

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.44
PhyloP100		0.98
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: rs11144047; hg19: chr9-77276405;