15-60489314-T-C

Position:

• chr15-60489314-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.*8141A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,118 control chromosomes in the GnomAD database, including 7,540 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 0.31 (7540 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RORA NM_134261.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.*8141A>G		3_prime_UTR_variant	11/11	ENST00000335670.11
RORA-AS1	NR_120342.1	n.289+723T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.*8141A>G		3_prime_UTR_variant	11/11	1	NM_134261.3
RORA-AS1	ENST00000559824.5	n.289+723T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47034 AN: 152000 Hom.: 7533 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.360

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.309 AC: 47059 AN: 152118 Hom.: 7540 Cov.: 32 AF XY: 0.302 AC XY: 22481 AN XY: 74364

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.356

Alfa AF: 0.333 Hom.: 19328

Bravo AF: 0.319

Asia WGS AF: 0.167 AC: 584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.70

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: rs3743266; hg19: chr15-60781513;