Menu
GeneBe

15-60499904-T-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_134261.3(RORA):c.1395A>T(p.Gly465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,600,684 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00098 ( 11 hom. )

Consequence

RORA
NM_134261.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.186
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-AS1 (HGNC:51410): (RORA antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 15-60499904-T-A is Benign according to our data. Variant chr15-60499904-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1675578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.186 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000977 (1415/1448426) while in subpopulation MID AF= 0.0225 (129/5722). AF 95% confidence interval is 0.0194. There are 11 homozygotes in gnomad4_exome. There are 762 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
High AC in GnomAd4 at 211 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RORANM_134261.3 linkuse as main transcriptc.1395A>T p.Gly465= synonymous_variant 10/11 ENST00000335670.11
RORA-AS1NR_120342.1 linkuse as main transcriptn.290-10504T>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RORAENST00000335670.11 linkuse as main transcriptc.1395A>T p.Gly465= synonymous_variant 10/111 NM_134261.3 P35398-2
RORA-AS1ENST00000559824.5 linkuse as main transcriptn.290-10504T>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00139
AC:
211
AN:
152140
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00550
Gnomad ASJ
AF:
0.0109
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.000911
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00135
AC:
336
AN:
248492
Hom.:
3
AF XY:
0.00151
AC XY:
203
AN XY:
134492
show subpopulations
Gnomad AFR exome
AF:
0.0000618
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.00865
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00112
Gnomad FIN exome
AF:
0.0000934
Gnomad NFE exome
AF:
0.00105
Gnomad OTH exome
AF:
0.00233
GnomAD4 exome
AF:
0.000977
AC:
1415
AN:
1448426
Hom.:
11
Cov.:
27
AF XY:
0.00106
AC XY:
762
AN XY:
721554
show subpopulations
Gnomad4 AFR exome
AF:
0.000576
Gnomad4 AMR exome
AF:
0.00245
Gnomad4 ASJ exome
AF:
0.0114
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00112
Gnomad4 FIN exome
AF:
0.0000941
Gnomad4 NFE exome
AF:
0.000604
Gnomad4 OTH exome
AF:
0.00164
GnomAD4 genome
AF:
0.00139
AC:
211
AN:
152258
Hom.:
1
Cov.:
32
AF XY:
0.00145
AC XY:
108
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00550
Gnomad4 ASJ
AF:
0.0109
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000911
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00163
Hom.:
0
Bravo
AF:
0.00151
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00219
EpiControl
AF:
0.00208

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024RORA-AS1: BS2 -
RORA-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 19, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
5.5
DANN
Benign
0.80

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: rs117458658; hg19: chr15-60792103; API