rs2290430

chr15-60499755-A-C

Variant summary

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

The NM_134261.3(RORA):c.1407+137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 534,268 control chromosomes in the GnomAD database, including 2,235 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 0.095 (695 hom., cov: 32)
  • Exomes 𝑓: 0.086 (1540 hom.)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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]

RORA-AS1 (HGNC:51410): (RORA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.1407+137T>G		intron_variant		ENST00000335670.11
RORA-AS1	NR_120342.1	n.290-10653A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.1407+137T>G		intron_variant		1	NM_134261.3
RORA-AS1	ENST00000559824.5	n.290-10653A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14395 AN: 152046 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0489

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0856 AC: 32689 AN: 382104 Hom.: 1540 AF XY: 0.0854 AC XY: 17138 AN XY: 200632

Gnomad4 AFR exome AF: 0.0989

Gnomad4 AMR exome AF: 0.0999

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0348

Gnomad4 SAS exome AF: 0.0600

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.0899

GnomAD4 genome AF: 0.0946 AC: 14397 AN: 152164 Hom.: 695 Cov.: 32 AF XY: 0.0936 AC XY: 6962 AN XY: 74398

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0494

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.0936

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0917 Hom.: 428

Bravo AF: 0.0968

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.067
Dann	Benign	0.64

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: rs2290430; hg19: chr15-60791954;