rs7177611

Variant names:

• chr15-61080560-G-A
• rs7177611
• NM_134261.3:c.166+148493C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-61080560-G-A
• chr15-61080560-G-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+148493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,002 control chromosomes in the GnomAD database, including 5,232 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 0.26 (5232 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 7 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)

LOC107984805 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+148493C>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+148493C>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39717 AN: 151884 Hom.: 5228 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.261 AC: 39748 AN: 152002 Hom.: 5232 Cov.: 32 AF XY: 0.255 AC XY: 18942 AN XY: 74274

African (AFR) AF: 0.267 AC: 11071 AN: 41444

American (AMR) AF: 0.244 AC: 3721 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3468

East Asian (EAS) AF: 0.143 AC: 740 AN: 5170

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4804

European-Finnish (FIN) AF: 0.214 AC: 2260 AN: 10572

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19220 AN: 67952

Other (OTH) AF: 0.259 AC: 545 AN: 2108

Alfa AF: 0.275 Hom.: 25231

Bravo AF: 0.266

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		-0.12
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: rs7177611; hg19: chr15-61372759;