rs12912233

Positions:

• chr15-60974897-C-T

Variant summary

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

The NM_134261.3(RORA):​c.166+254156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,112 control chromosomes in the GnomAD database, including 11,536 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 0.38 (11536 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+254156G>A		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1752+254156G>A		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+254156G>A		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57229 AN: 151994 Hom.: 11533 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.376 AC: 57249 AN: 152112 Hom.: 11536 Cov.: 33 AF XY: 0.378 AC XY: 28095 AN XY: 74386

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.384

Alfa AF: 0.427 Hom.: 16556

Bravo AF: 0.355

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.57

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: rs12912233; hg19: chr15-61267096;