rs11144020

Variant names:

• chr9-74603429-C-A
• rs11144020
• NM_006914.4:c.8-26853C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-74603429-C-A
• chr9-74603429-C-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.8-26853C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,896 control chromosomes in the GnomAD database, including 16,527 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 0.46 (16527 hom., cov: 31)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-26853C>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.8-26853C>A		intron_variant	Intron 1 of 9	1	NM_006914.4	ENSP00000366093.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69896 AN: 151778 Hom.: 16524 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.460 AC: 69931 AN: 151896 Hom.: 16527 Cov.: 31 AF XY: 0.464 AC XY: 34444 AN XY: 74232

African (AFR) AF: 0.380 AC: 15723 AN: 41398

American (AMR) AF: 0.441 AC: 6735 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3470

East Asian (EAS) AF: 0.770 AC: 3965 AN: 5152

South Asian (SAS) AF: 0.491 AC: 2362 AN: 4812

European-Finnish (FIN) AF: 0.524 AC: 5529 AN: 10546

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32282 AN: 67940

Other (OTH) AF: 0.461 AC: 967 AN: 2096

Alfa AF: 0.472 Hom.: 75033

Bravo AF: 0.452

Asia WGS AF: 0.555 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		0.058
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: rs11144020; hg19: chr9-77218345;