NM_134261.3:c.197-17225T>C

Variant names:

• chr15-60549076-A-G
• rs2028122
• NM_134261.3:c.197-17225T>C

Variant summary

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

The NM_134261.3(RORA):​c.197-17225T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,098 control chromosomes in the GnomAD database, including 23,910 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 0.52 (23910 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 22 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-17225T>C		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.197-17225T>C		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79568 AN: 151980 Hom.: 23893 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.523 AC: 79594 AN: 152098 Hom.: 23910 Cov.: 32 AF XY: 0.536 AC XY: 39820 AN XY: 74332

African (AFR) AF: 0.222 AC: 9221 AN: 41484

American (AMR) AF: 0.633 AC: 9688 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3468

East Asian (EAS) AF: 0.878 AC: 4555 AN: 5190

South Asian (SAS) AF: 0.772 AC: 3723 AN: 4822

European-Finnish (FIN) AF: 0.704 AC: 7437 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41141 AN: 67960

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.577 Hom.: 49233

Bravo AF: 0.502

Asia WGS AF: 0.778 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		0.023
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: rs2028122; hg19: chr15-60841275;