rs10869430

Positions:

• chr9-74621347-G-A
• chr9-74621347-G-T

Variant summary

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

The NM_006914.4(RORB):​c.8-8935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,924 control chromosomes in the GnomAD database, including 8,343 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 0.32 (8343 hom., cov: 33)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-8935G>A		intron_variant		ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.40+5708G>A		intron_variant			NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.8-8935G>A		intron_variant		1	NM_006914.4	ENSP00000366093.2
RORB	ENST00000396204.2	c.40+5708G>A		intron_variant		1		ENSP00000379507.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48610 AN: 151806 Hom.: 8349 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.320 AC: 48605 AN: 151924 Hom.: 8343 Cov.: 33 AF XY: 0.324 AC XY: 24048 AN XY: 74232

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.320

Alfa AF: 0.345 Hom.: 12442

Bravo AF: 0.312

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.64

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: rs10869430; hg19: chr9-77236263;