rs10869406

Positions:

• chr9-74499358-G-A
• chr9-74499358-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.7+1375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,844 control chromosomes in the GnomAD database, including 13,156 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 0.41 (13156 hom., cov: 31)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORB	NM_006914.4	c.7+1375G>A		intron_variant		ENST00000376896.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORB	ENST00000376896.8	c.7+1375G>A		intron_variant		1	NM_006914.4	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62021 AN: 151726 Hom.: 13164 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.409 AC: 62046 AN: 151844 Hom.: 13156 Cov.: 31 AF XY: 0.413 AC XY: 30615 AN XY: 74202

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.398

Alfa AF: 0.383 Hom.: 8411

Bravo AF: 0.411

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10869406; hg19: chr9-77114274;