rs1869486

Positions:

• chr15-60502608-A-G
• chr15-60502608-A-T

Variant summary

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

The NM_134261.3(RORA):​c.1183+152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 638,020 control chromosomes in the GnomAD database, including 208,523 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 0.75 (43611 hom., cov: 32)
  • Exomes 𝑓: 0.82 (164912 hom.)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.1183+152T>C		intron_variant		ENST00000335670.11	NP_599023.1
RORA-AS1	NR_120342.1	n.290-7800A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.1183+152T>C		intron_variant		1	NM_134261.3	ENSP00000335087
RORA-AS1	ENST00000559824.5	n.290-7800A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113589 AN: 152022 Hom.: 43578 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.821 AC: 398844 AN: 485880 Hom.: 164912 AF XY: 0.824 AC XY: 214472 AN XY: 260202

Gnomad4 AFR exome AF: 0.560

Gnomad4 AMR exome AF: 0.829

Gnomad4 ASJ exome AF: 0.793

Gnomad4 EAS exome AF: 0.963

Gnomad4 SAS exome AF: 0.887

Gnomad4 FIN exome AF: 0.859

Gnomad4 NFE exome AF: 0.804

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.747 AC: 113673 AN: 152140 Hom.: 43611 Cov.: 32 AF XY: 0.753 AC XY: 56044 AN XY: 74394

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.760

Alfa AF: 0.798 Hom.: 22078

Bravo AF: 0.734

Asia WGS AF: 0.897 AC: 3119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.8
DANN	Benign	0.84

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: rs1869486; hg19: chr15-60794807;