9-74649312-T-A

Position:

• chr9-74649312-T-A

Variant summary

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

The NM_006914.4(RORB):​c.637+6497T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,918 control chromosomes in the GnomAD database, including 4,109 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 0.23 (4109 hom., cov: 31)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORB	NM_006914.4	c.637+6497T>A		intron_variant		ENST00000376896.8
RORB	NM_001365023.1	c.670+6497T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORB	ENST00000376896.8	c.637+6497T>A		intron_variant		1	NM_006914.4	P1
RORB	ENST00000396204.2	c.670+6497T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34246 AN: 151800 Hom.: 4102 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.226 AC: 34281 AN: 151918 Hom.: 4109 Cov.: 31 AF XY: 0.228 AC XY: 16943 AN XY: 74260

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.228

Alfa AF: 0.247 Hom.: 609

Bravo AF: 0.220

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.77

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: rs3903529; hg19: chr9-77264228;