15-60608764-C-T

Variant names:

• chr15-60608764-C-T
• rs980000
• NM_134261.3:c.196+69893G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.196+69893G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,064 control chromosomes in the GnomAD database, including 1,686 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 0.11 (1686 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 6 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.196+69893G>A		intron_variant	Intron 2 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.196+69893G>A		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16151 AN: 151946 Hom.: 1682 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0847

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16175 AN: 152064 Hom.: 1686 Cov.: 32 AF XY: 0.105 AC XY: 7770 AN XY: 74338

African (AFR) AF: 0.270 AC: 11164 AN: 41424

American (AMR) AF: 0.0643 AC: 982 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0621 AC: 299 AN: 4812

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10586

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2938 AN: 67994

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.110 Hom.: 843

Bravo AF: 0.116

Asia WGS AF: 0.0420 AC: 146 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	10
DANN	Benign	0.74
PhyloP100		0.095
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: rs980000; hg19: chr15-60900963;