rs4774388

chr15-61174799-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+54254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,030 control chromosomes in the GnomAD database, including 49,415 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 0.80 (49415 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.166+54254G>A		intron_variant		ENST00000335670.11
RORA	XM_047432928.1	c.-1752+54254G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.166+54254G>A		intron_variant		1	NM_134261.3

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121959 AN: 151912 Hom.: 49390 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.803 AC: 122029 AN: 152030 Hom.: 49415 Cov.: 31 AF XY: 0.796 AC XY: 59177 AN XY: 74302

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.801

Alfa AF: 0.835 Hom.: 112664

Bravo AF: 0.793

Asia WGS AF: 0.647 AC: 2249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.94
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: rs4774388; hg19: chr15-61466998;