9-74634466-C-T

Variant summary

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

The NM_006914.4(RORB):c.94-165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,108 control chromosomes in the GnomAD database, including 7,125 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 0.30 (7125 hom., cov: 33)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORB	NM_006914.4	c.94-165C>T		intron_variant		ENST00000376896.8
RORB	NM_001365023.1	c.127-165C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORB	ENST00000376896.8	c.94-165C>T		intron_variant		1	NM_006914.4	P1
RORB	ENST00000396204.2	c.127-165C>T		intron_variant		1
	ENST00000658390.1	n.2867-1344G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44937 AN: 151990 Hom.: 7113 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.296 AC: 44969 AN: 152108 Hom.: 7125 Cov.: 33 AF XY: 0.302 AC XY: 22483 AN XY: 74338

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.292

Alfa AF: 0.311 Hom.: 4287

Bravo AF: 0.292

Asia WGS AF: 0.388 AC: 1346 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.0
Dann	Benign	0.32

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: rs3750420; hg19: chr9-77249382;