NM_134261.3:c.1395A>T

Variant names:

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.Gly465Gly) 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

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

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 links:

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

RORA-AS1 links:

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 rank	MANE	Protein	UniProt
RORA	NM_134261.3 link	c.1395A>T	p.Gly465Gly	synonymous_variant	Exon 10 of 11	ENST00000335670.11	NP_599023.1	P35398-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11 link	c.1395A>T	p.Gly465Gly	synonymous_variant	Exon 10 of 11	1	NM_134261.3	ENSP00000335087.6		P35398-2

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152140

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00151

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00219

EpiControl

AF:

0.00208

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RORA: BP4, BP7, BS2; RORA-AS1: BS2 -

RORA-related disorder

Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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.

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