Variant 15-60497599-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_134261.3(RORA):c.1428C>A(p.Thr476Thr) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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 links:

RORA-AS1 (HGNC:):

RORA-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RORA	NM_134261.3 linkuse as main transcript	c.1428C>A	p.Thr476Thr	synonymous_variant	11/11	ENST00000335670.11	NP_599023.1	P35398-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11 linkuse as main transcript	c.1428C>A	p.Thr476Thr	synonymous_variant	11/11	1	NM_134261.3	ENSP00000335087.6		P35398-2

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

144597

AN:

152150

Hom.:

69084

Cov.:

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.:

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.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual developmental disorder with or without epilepsy or cerebellar ataxia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over