dbSNP rs1869486: RORA:c.1183+152T>C (chr15-60502608-A-G) – 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.1183+152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 638,020 control chromosomes in the GnomAD database, including 208,523 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 0.75 ( 43611 hom., cov: 32)

Exomes 𝑓: 0.82 ( 164912 hom. )

Consequence

RORA
NM_134261.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

14 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:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3 link	c.1183+152T>C		intron_variant	Intron 8 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.1183+152T>C		intron_variant	Intron 8 of 10	1	NM_134261.3	ENSP00000335087.6		P35398-2

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113589

AN:

152022

Hom.:

43578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.821

Gnomad AMR

AF:

0.794

Gnomad ASJ

AF:

0.786

Gnomad EAS

AF:

0.950

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.758

GnomAD4 exome

AF:

0.821

AC:

398844

AN:

485880

Hom.:

164912

AF XY:

0.824

AC XY:

214472

AN XY:

260202

show subpopulations

African (AFR)

AF:

0.560

AC:

7424

AN:

13250

American (AMR)

AF:

0.829

AC:

17773

AN:

21436

Ashkenazi Jewish (ASJ)

AF:

0.793

AC:

11062

AN:

13946

East Asian (EAS)

AF:

0.963

AC:

31650

AN:

32854

South Asian (SAS)

AF:

0.887

AC:

40673

AN:

45872

European-Finnish (FIN)

AF:

0.859

AC:

31517

AN:

36698

Middle Eastern (MID)

AF:

0.768

AC:

1549

AN:

2018

European-Non Finnish (NFE)

AF:

0.804

AC:

235603

AN:

292886

Other (OTH)

AF:

0.802

AC:

21593

AN:

26920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

3160

6320

9479

12639

15799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.747

AC:

113673

AN:

152140

Hom.:

43611

Cov.:

AF XY:

0.753

AC XY:

56044

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.560

AC:

23233

AN:

41456

American (AMR)

AF:

0.795

AC:

12145

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

2729

AN:

3470

East Asian (EAS)

AF:

0.950

AC:

4923

AN:

5184

South Asian (SAS)

AF:

0.893

AC:

4308

AN:

4822

European-Finnish (FIN)

AF:

0.856

AC:

9063

AN:

10588

Middle Eastern (MID)

AF:

0.699

AC:

204

AN:

292

European-Non Finnish (NFE)

AF:

0.804

AC:

54712

AN:

68016

Other (OTH)

AF:

0.760

AC:

1609

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1404

2809

4213

5618

7022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.801

Hom.:

30419

Bravo

AF:

0.734

Asia WGS

AF:

0.897

AC:

3119

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.8

(source)

DANN

Benign

0.84

PhyloP100

1.3

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

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rs1869486

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