rs8042149

Variant names:

• chr15-60832754-T-G
• rs8042149
• NM_134261.3:c.167-154068A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with or without epilepsy or cerebellar ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.167-154068A>C		intron	N/A	NP_599023.1	P35398-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.167-154068A>C		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000551975.5	TSL:3	n.80-154068A>C		intron	N/A	ENSP00000449482.1	H0YII6
	RORA	ENST00000557822.5	TSL:4	n.192-154068A>C		intron	N/A

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

African (AFR) AF: 0.256 AC: 10623 AN: 41460

American (AMR) AF: 0.437 AC: 6672 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1917 AN: 3466

East Asian (EAS) AF: 0.486 AC: 2509 AN: 5164

South Asian (SAS) AF: 0.486 AC: 2343 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4866 AN: 10534

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37138 AN: 67930

Other (OTH) AF: 0.473 AC: 997 AN: 2108

Alfa AF: 0.521 Hom.: 45321

Bravo AF: 0.436

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.63
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8042149; hg19: chr15-61124953;