15-60531218-T-C

Position:

• chr15-60531218-T-C

Variant summary

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

The NM_134261.3(RORA):​c.282+548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 153,200 control chromosomes in the GnomAD database, including 888 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 0.099 (878 hom., cov: 33)
  • Exomes 𝑓: 0.13 (10 hom.)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.282+548A>G		intron_variant		ENST00000335670.11	NP_599023.1
RORA-AS1	NR_120342.1	n.415+20685T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.282+548A>G		intron_variant		1	NM_134261.3	ENSP00000335087
RORA-AS1	ENST00000559824.5	n.415+20685T>C		intron_variant, non_coding_transcript_variant		3
	ENST00000560280.1	n.79+1167T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15088 AN: 152164 Hom.: 878 Cov.: 33

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.0958

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.133 AC: 122 AN: 918 Hom.: 10 Cov.: 0 AF XY: 0.130 AC XY: 77 AN XY: 594

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0667

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0990 AC: 15080 AN: 152282 Hom.: 878 Cov.: 33 AF XY: 0.0961 AC XY: 7159 AN XY: 74462

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.0885

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.0998

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.113

Alfa AF: 0.132 Hom.: 1647

Bravo AF: 0.0984

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.85

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: rs10519052; hg19: chr15-60823417;