chr15-60982031-C-T

Position:

• chr15-60982031-C-T

Variant summary

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

The NM_134261.3(RORA):​c.166+247022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,100 control chromosomes in the GnomAD database, including 5,046 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 0.25 (5046 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+247022G>A		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1752+247022G>A		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+247022G>A		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38373 AN: 151982 Hom.: 5036 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.253 AC: 38411 AN: 152100 Hom.: 5046 Cov.: 33 AF XY: 0.257 AC XY: 19139 AN XY: 74356

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.240

Alfa AF: 0.230 Hom.: 977

Bravo AF: 0.245

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.64

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: rs7495128; hg19: chr15-61274230;