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15-60497599-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_134261.3(RORA):c.1428C>A(p.Thr476=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,612,332 control chromosomes in the GnomAD database, including 790,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.95 ( 69132 hom., cov: 31)
Exomes 𝑓: 0.99 ( 721124 hom. )

Consequence

RORA
NM_134261.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0770
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 15-60497599-G-T is Benign according to our data. Variant chr15-60497599-G-T is described in ClinVar as [Benign]. Clinvar id is 1327966.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.077 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RORANM_134261.3 linkuse as main transcriptc.1428C>A p.Thr476= synonymous_variant 11/11 ENST00000335670.11
RORA-AS1NR_120342.1 linkuse as main transcriptn.289+9008G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RORAENST00000335670.11 linkuse as main transcriptc.1428C>A p.Thr476= synonymous_variant 11/111 NM_134261.3 P35398-2
RORA-AS1ENST00000559824.5 linkuse as main transcriptn.289+9008G>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.950
AC:
144597
AN:
152150
Hom.:
69084
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.831
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.980
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.983
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
1.00
Gnomad NFE
AF:
0.998
Gnomad OTH
AF:
0.967
GnomAD3 exomes
AF:
0.985
AC:
246683
AN:
250322
Hom.:
121761
AF XY:
0.988
AC XY:
133860
AN XY:
135430
show subpopulations
Gnomad AFR exome
AF:
0.827
Gnomad AMR exome
AF:
0.992
Gnomad ASJ exome
AF:
1.00
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
0.987
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
0.999
Gnomad OTH exome
AF:
0.994
GnomAD4 exome
AF:
0.994
AC:
1450619
AN:
1460064
Hom.:
721124
Cov.:
39
AF XY:
0.994
AC XY:
722014
AN XY:
726500
show subpopulations
Gnomad4 AFR exome
AF:
0.826
Gnomad4 AMR exome
AF:
0.991
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
0.986
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
0.999
Gnomad4 OTH exome
AF:
0.987
GnomAD4 genome
AF:
0.950
AC:
144704
AN:
152268
Hom.:
69132
Cov.:
31
AF XY:
0.953
AC XY:
70926
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.831
Gnomad4 AMR
AF:
0.980
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.984
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
0.998
Gnomad4 OTH
AF:
0.968
Alfa
AF:
0.976
Hom.:
47268
Bravo
AF:
0.944
Asia WGS
AF:
0.990
AC:
3442
AN:
3478
EpiCase
AF:
0.999
EpiControl
AF:
0.998

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual developmental disorder with or without epilepsy or cerebellar ataxia Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
1.4
DANN
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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: rs11071539; hg19: chr15-60789798; API