rs7177846

Variant names:

• chr15-61198841-A-G
• rs7177846
• NM_134261.3:c.166+30212T>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.166+30212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,838 control chromosomes in the GnomAD database, including 8,718 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 0.33 (8718 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 8 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

LOC105370841 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+30212T>C		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
LOC105370841	XR_001751772.2	n.22153T>C		non_coding_transcript_exon_variant	Exon 3 of 3
LOC105370841	XR_007064661.1	n.22389T>C		non_coding_transcript_exon_variant	Exon 2 of 2
RORA	XM_047432928.1	c.-1752+30212T>C		intron_variant	Intron 1 of 10		XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+30212T>C		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50755 AN: 151720 Hom.: 8706 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.335 AC: 50793 AN: 151838 Hom.: 8718 Cov.: 31 AF XY: 0.333 AC XY: 24733 AN XY: 74204

African (AFR) AF: 0.314 AC: 12997 AN: 41412

American (AMR) AF: 0.282 AC: 4297 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1340 AN: 3416

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5154

South Asian (SAS) AF: 0.303 AC: 1458 AN: 4814

European-Finnish (FIN) AF: 0.368 AC: 3885 AN: 10556

Middle Eastern (MID) AF: 0.352 AC: 102 AN: 290

European-Non Finnish (NFE) AF: 0.343 AC: 23294 AN: 67928

Other (OTH) AF: 0.327 AC: 686 AN: 2098

Alfa AF: 0.334 Hom.: 15870

Bravo AF: 0.330

Asia WGS AF: 0.368 AC: 1279 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	0.15
DANN	Benign	0.33
PhyloP100		-1.1
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: rs7177846; hg19: chr15-61491040;