15-60602766-C-T

Variant names:

• chr15-60602766-C-T
• rs340029
• NM_134261.3:c.197-70915G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.197-70915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,090 control chromosomes in the GnomAD database, including 37,580 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 0.69 (37580 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-70915G>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.197-70915G>A		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105569 AN: 151972 Hom.: 37529 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.695 AC: 105687 AN: 152090 Hom.: 37580 Cov.: 32 AF XY: 0.699 AC XY: 51966 AN XY: 74346

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.667

Alfa AF: 0.631 Hom.: 34421

Bravo AF: 0.695

Asia WGS AF: 0.760 AC: 2640 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.84
DANN	Benign	0.51

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: rs340029; hg19: chr15-60894965;