rs17691363

Positions:

• chr9-74617578-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_006914.4(RORB):​c.8-12704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 152,246 control chromosomes in the GnomAD database, including 106 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 0.030 (106 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0302 (4593/152246) while in subpopulation NFE AF= 0.0477 (3246/68012). AF 95% confidence interval is 0.0464. There are 106 homozygotes in gnomad4. There are 2190 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4593 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-12704A>G		intron_variant		ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.40+1939A>G		intron_variant			NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.8-12704A>G		intron_variant		1	NM_006914.4	ENSP00000366093	P1
RORB	ENST00000396204.2	c.40+1939A>G		intron_variant		1		ENSP00000379507

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4600 AN: 152128 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0302 AC: 4593 AN: 152246 Hom.: 106 Cov.: 32 AF XY: 0.0294 AC XY: 2190 AN XY: 74438

Gnomad4 AFR AF: 0.00732

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.0432 Hom.: 215

Bravo AF: 0.0272

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.73

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: rs17691363; hg19: chr9-77232494;