15-60528610-A-G

Variant names:

• chr15-60528610-A-G
• rs1898413
• NM_134261.3:c.282+3156T>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+3156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,062 control chromosomes in the GnomAD database, including 23,721 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 0.51 (23717 hom., cov: 31)
  • Exomes 𝑓: 0.69 (4 hom.)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.282+3156T>C		intron_variant	Intron 3 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.282+3156T>C		intron_variant	Intron 3 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76957 AN: 151928 Hom.: 23701 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.688 AC: 11 AN: 16 Hom.: 4 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.583

GnomAD4 genome AF: 0.506 AC: 76978 AN: 152046 Hom.: 23717 Cov.: 31 AF XY: 0.519 AC XY: 38600 AN XY: 74320

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.519

Alfa AF: 0.578 Hom.: 24458

Bravo AF: 0.481

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.66

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: rs1898413; hg19: chr15-60820809;