rs968357

chr9-74649873-T-C

Variant summary

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

The NM_006914.4(RORB):c.637+7058T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,184 control chromosomes in the GnomAD database, including 1,855 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 0.14 (1855 hom., cov: 33)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORB	NM_006914.4	c.637+7058T>C		intron_variant		ENST00000376896.8
RORB	NM_001365023.1	c.670+7058T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORB	ENST00000376896.8	c.637+7058T>C		intron_variant		1	NM_006914.4	P1
RORB	ENST00000396204.2	c.670+7058T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21421 AN: 152066 Hom.: 1855 Cov.: 33

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.141 AC: 21416 AN: 152184 Hom.: 1855 Cov.: 33 AF XY: 0.142 AC XY: 10583 AN XY: 74426

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.141

Alfa AF: 0.167 Hom.: 1169

Bravo AF: 0.134

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.3
Dann	Benign	0.37

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: rs968357; hg19: chr9-77264789;