rs7495128

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_134261.3(RORA):​c.166+247022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,100 control chromosomes in the GnomAD database, including 5,046 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 0.25 ( 5046 hom., cov: 33)

Consequence

RORA
NM_134261.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

3 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RORANM_134261.3 linkc.166+247022G>A intron_variant Intron 1 of 10 ENST00000335670.11 NP_599023.1 P35398-2
RORAXM_047432928.1 linkc.-1752+247022G>A intron_variant Intron 1 of 10 XP_047288884.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RORAENST00000335670.11 linkc.166+247022G>A intron_variant Intron 1 of 10 1 NM_134261.3 ENSP00000335087.6 P35398-2

Frequencies

GnomAD3 genomes
AF:
0.252
AC:
38373
AN:
151982
Hom.:
5036
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.289
Gnomad AMI
AF:
0.156
Gnomad AMR
AF:
0.242
Gnomad ASJ
AF:
0.196
Gnomad EAS
AF:
0.332
Gnomad SAS
AF:
0.328
Gnomad FIN
AF:
0.312
Gnomad MID
AF:
0.168
Gnomad NFE
AF:
0.217
Gnomad OTH
AF:
0.240
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.253
AC:
38411
AN:
152100
Hom.:
5046
Cov.:
33
AF XY:
0.257
AC XY:
19139
AN XY:
74356
show subpopulations
African (AFR)
AF:
0.289
AC:
11995
AN:
41464
American (AMR)
AF:
0.242
AC:
3693
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.196
AC:
679
AN:
3470
East Asian (EAS)
AF:
0.332
AC:
1723
AN:
5182
South Asian (SAS)
AF:
0.326
AC:
1574
AN:
4826
European-Finnish (FIN)
AF:
0.312
AC:
3294
AN:
10560
Middle Eastern (MID)
AF:
0.180
AC:
53
AN:
294
European-Non Finnish (NFE)
AF:
0.217
AC:
14752
AN:
67994
Other (OTH)
AF:
0.240
AC:
506
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1510
3019
4529
6038
7548
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
402
804
1206
1608
2010
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.230
Hom.:
977
Bravo
AF:
0.245
Asia WGS
AF:
0.337
AC:
1172
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
3.3
DANN
Benign
0.64
PhyloP100
0.086
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

Publications

Other links and lift over

dbSNP: rs7495128; hg19: chr15-61274230; API