rs7495128

Variant summary

Our verdict is Benign. Variant got -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
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
RORANM_134261.3 linkuse as main transcriptc.166+247022G>A intron_variant ENST00000335670.11
RORAXM_047432928.1 linkuse as main transcriptc.-1752+247022G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RORAENST00000335670.11 linkuse as main transcriptc.166+247022G>A intron_variant 1 NM_134261.3 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
Gnomad4 AFR
AF:
0.289
Gnomad4 AMR
AF:
0.242
Gnomad4 ASJ
AF:
0.196
Gnomad4 EAS
AF:
0.332
Gnomad4 SAS
AF:
0.326
Gnomad4 FIN
AF:
0.312
Gnomad4 NFE
AF:
0.217
Gnomad4 OTH
AF:
0.240
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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7495128; hg19: chr15-61274230; API