15-61219962-T-C

Variant summary

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

The NM_134261.3(RORA):c.166+9091A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,168 control chromosomes in the GnomAD database, including 3,009 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 0.19 (3009 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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]

LOC105370841 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.166+9091A>G		intron_variant		ENST00000335670.11
LOC105370841	XR_001751772.2	n.1032A>G		non_coding_transcript_exon_variant	3/3
RORA	XM_047432928.1	c.-1752+9091A>G		intron_variant
LOC105370841	XR_007064661.1	n.1268A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.166+9091A>G		intron_variant		1	NM_134261.3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28574 AN: 152046 Hom.: 3010 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.188 AC: 28608 AN: 152168 Hom.: 3009 Cov.: 32 AF XY: 0.190 AC XY: 14117 AN XY: 74410

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.167

Alfa AF: 0.150 Hom.: 1797

Bravo AF: 0.190

Asia WGS AF: 0.227 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.50

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: rs11631786; hg19: chr15-61512161;