rs17270446

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_134261.3(RORA):​c.167-102917G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,172 control chromosomes in the GnomAD database, including 7,233 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 0.28 ( 7233 hom., cov: 29)

Consequence

RORA
NM_134261.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.58
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=-0.63).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RORANM_134261.3 linkuse as main transcriptc.167-102917G>C intron_variant ENST00000335670.11
RORAXM_047432928.1 linkuse as main transcriptc.-1751-102917G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RORAENST00000335670.11 linkuse as main transcriptc.167-102917G>C intron_variant 1 NM_134261.3 P35398-2

Frequencies

GnomAD3 genomes
AF:
0.283
AC:
42786
AN:
151054
Hom.:
7234
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.324
Gnomad AMR
AF:
0.415
Gnomad ASJ
AF:
0.323
Gnomad EAS
AF:
0.181
Gnomad SAS
AF:
0.281
Gnomad FIN
AF:
0.300
Gnomad MID
AF:
0.274
Gnomad NFE
AF:
0.366
Gnomad OTH
AF:
0.298
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.283
AC:
42782
AN:
151172
Hom.:
7233
Cov.:
29
AF XY:
0.282
AC XY:
20814
AN XY:
73740
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.415
Gnomad4 ASJ
AF:
0.323
Gnomad4 EAS
AF:
0.180
Gnomad4 SAS
AF:
0.280
Gnomad4 FIN
AF:
0.300
Gnomad4 NFE
AF:
0.366
Gnomad4 OTH
AF:
0.295
Alfa
AF:
0.211
Hom.:
515
Bravo
AF:
0.285
Asia WGS
AF:
0.243
AC:
844
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.46

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: rs17270446; hg19: chr15-61073802; API