dbSNP rs2290430: RORA:c.1407+137T>G (chr15-60499755-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_134261.3(RORA):c.1407+137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 534,268 control chromosomes in the GnomAD database, including 2,235 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 0.095 ( 695 hom., cov: 32)

Exomes 𝑓: 0.086 ( 1540 hom. )

Consequence

RORA
NM_134261.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3 link	c.1407+137T>G		intron_variant	Intron 10 of 10	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.1407+137T>G		intron_variant	Intron 10 of 10	1	NM_134261.3	ENSP00000335087.6		P35398-2

Frequencies

GnomAD3 genomes

AF:

0.0947

AC:

14395

AN:

152046

Hom.:

696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.0489

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0788

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0937

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.0856

AC:

32689

AN:

382104

Hom.:

1540

AF XY:

0.0854

AC XY:

17138

AN XY:

200632

show subpopulations

African (AFR)

AF:

0.0989

AC:

964

AN:

9748

American (AMR)

AF:

0.0999

AC:

1137

AN:

11378

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

1468

AN:

11894

East Asian (EAS)

AF:

0.0348

AC:

936

AN:

26924

South Asian (SAS)

AF:

0.0600

AC:

1691

AN:

28200

European-Finnish (FIN)

AF:

0.0689

AC:

2296

AN:

33324

Middle Eastern (MID)

AF:

0.105

AC:

327

AN:

3124

European-Non Finnish (NFE)

AF:

0.0930

AC:

21830

AN:

234830

Other (OTH)

AF:

0.0899

AC:

2040

AN:

22682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1399

2798

4197

5596

6995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0946

AC:

14397

AN:

152164

Hom.:

695

Cov.:

AF XY:

0.0936

AC XY:

6962

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.101

AC:

4176

AN:

41504

American (AMR)

AF:

0.109

AC:

1660

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

432

AN:

3468

East Asian (EAS)

AF:

0.0494

AC:

256

AN:

5178

South Asian (SAS)

AF:

0.0590

AC:

284

AN:

4810

European-Finnish (FIN)

AF:

0.0788

AC:

834

AN:

10588

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0936

AC:

6368

AN:

68012

Other (OTH)

AF:

0.106

AC:

223

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

664

1328

1991

2655

3319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0921

Hom.:

1312

Bravo

AF:

0.0968

Asia WGS

AF:

0.0600

AC:

210

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.067

(source)

DANN

Benign

0.64

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over