rs11144020

Positions:

• chr9-74603429-C-A
• chr9-74603429-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-26853C>A		intron_variant		ENST00000376896.8	NP_008845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.8-26853C>A		intron_variant		1	NM_006914.4	ENSP00000366093	P1

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

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.461

Alfa AF: 0.476 Hom.: 35501

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11144020; hg19: chr9-77218345;