rs8025689

Positions:

• chr15-60767062-G-C

Variant summary

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

The NM_134261.3(RORA):​c.167-88376C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,154 control chromosomes in the GnomAD database, including 3,586 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 0.20 (3586 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

Genes affected

RORA (HGNC:10258): (RAR related orphan receptor A) The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It 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, as well as with NM23-1, the product of a tumor metastasis suppressor candidate gene. Also, it has been shown to aid in the transcriptional regulation of some genes involved in circadian rhythm. Four transcript variants encoding different isoforms have been described for this gene. [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 (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-88376C>G		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-88376C>G		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-88376C>G		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30617 AN: 152036 Hom.: 3582 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.201 AC: 30647 AN: 152154 Hom.: 3586 Cov.: 32 AF XY: 0.201 AC XY: 14943 AN XY: 74382

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.183

Alfa AF: 0.179 Hom.: 341

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.76

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: rs8025689; hg19: chr15-61059261;