rs11144062

Positions:

• chr9-74684824-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006914.4(RORB):​c.1225-639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,088 control chromosomes in the GnomAD database, including 2,503 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 0.17 (2503 hom., cov: 31)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORB	NM_006914.4	c.1225-639G>A		intron_variant		ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.1258-639G>A		intron_variant			NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.1225-639G>A		intron_variant		1	NM_006914.4	ENSP00000366093	P1
RORB	ENST00000396204.2	c.1258-639G>A		intron_variant		1		ENSP00000379507

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26076 AN: 151968 Hom.: 2502 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.171 AC: 26078 AN: 152088 Hom.: 2503 Cov.: 31 AF XY: 0.170 AC XY: 12653 AN XY: 74342

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.171

Alfa AF: 0.182 Hom.: 5237

Bravo AF: 0.166

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.70

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: rs11144062; hg19: chr9-77299740;