15-60489314-T-C

Variant names:

• chr15-60489314-T-C
• rs3743266
• NM_134261.3:c.*8141A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 60 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.*8141A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.*8141A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_134261.3	ENSP00000335087.6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.325 AC: 13495 AN: 41482

American (AMR) AF: 0.300 AC: 4576 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3468

East Asian (EAS) AF: 0.163 AC: 847 AN: 5182

South Asian (SAS) AF: 0.154 AC: 742 AN: 4824

European-Finnish (FIN) AF: 0.222 AC: 2353 AN: 10588

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22444 AN: 67980

Other (OTH) AF: 0.356 AC: 752 AN: 2112

Alfa AF: 0.327 Hom.: 36330

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
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3743266; hg19: chr15-60781513;