rs8042149

Positions:

• chr15-60832754-T-G

Variant summary

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

The NM_134261.3(RORA):​c.167-154068A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,974 control chromosomes in the GnomAD database, including 16,302 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 0.45 (16302 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-154068A>C		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-154068A>C		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-154068A>C		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67692 AN: 151856 Hom.: 16298 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.445 AC: 67696 AN: 151974 Hom.: 16302 Cov.: 31 AF XY: 0.441 AC XY: 32749 AN XY: 74286

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.473

Alfa AF: 0.533 Hom.: 31354

Bravo AF: 0.436

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.63

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: rs8042149; hg19: chr15-61124953;