chr15-60757370-A-C

Variant names:

• chr15-60757370-A-C
• rs7183955
• NM_134261.3:c.167-78684T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.167-78684T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,306 control chromosomes in the GnomAD database, including 4,846 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 0.24 (4846 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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.167-78684T>G		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.167-78684T>G		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000551975.5	TSL:3	n.80-78684T>G		intron	N/A	ENSP00000449482.1	H0YII6
	RORA	ENST00000557822.5	TSL:4	n.192-78684T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36760 AN: 151188 Hom.: 4842 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.243 AC: 36801 AN: 151306 Hom.: 4846 Cov.: 32 AF XY: 0.243 AC XY: 17928 AN XY: 73850

African (AFR) AF: 0.358 AC: 14776 AN: 41236

American (AMR) AF: 0.157 AC: 2387 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 702 AN: 3462

East Asian (EAS) AF: 0.231 AC: 1188 AN: 5146

South Asian (SAS) AF: 0.301 AC: 1440 AN: 4778

European-Finnish (FIN) AF: 0.233 AC: 2428 AN: 10440

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13202 AN: 67768

Other (OTH) AF: 0.221 AC: 461 AN: 2090

Alfa AF: 0.207 Hom.: 10131

Bravo AF: 0.236

Asia WGS AF: 0.276 AC: 957 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.86
PhyloP100		-1.6
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: rs7183955; hg19: chr15-61049569;