dbSNP rs10519052: RORA:n.765A>G (chr15-60531218-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000558234.1(RORA):n.765A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 153,200 control chromosomes in the GnomAD database, including 888 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 0.099 ( 878 hom., cov: 33)

Exomes 𝑓: 0.13 ( 10 hom. )

Consequence

RORA
ENST00000558234.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

8 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3 link	c.282+548A>G		intron_variant	Intron 3 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.282+548A>G		intron_variant	Intron 3 of 10	1	NM_134261.3	ENSP00000335087.6		P35398-2

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15088

AN:

152164

Hom.:

878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.0958

Gnomad AMR

AF:

0.0888

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0459

Gnomad FIN

AF:

0.0998

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.133

AC:

122

AN:

918

Hom.:

Cov.:

AF XY:

0.130

AC XY:

AN XY:

594

show subpopulations

African (AFR)

AF:

0.111

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.0667

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.107

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.143

AC:

107

AN:

750

Other (OTH)

AF:

0.111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0990

AC:

15080

AN:

152282

Hom.:

878

Cov.:

AF XY:

0.0961

AC XY:

7159

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0445

AC:

1851

AN:

41576

American (AMR)

AF:

0.0885

AC:

1354

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

412

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

552

AN:

5178

South Asian (SAS)

AF:

0.0460

AC:

222

AN:

4830

European-Finnish (FIN)

AF:

0.0998

AC:

1058

AN:

10600

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9248

AN:

68016

Other (OTH)

AF:

0.113

AC:

239

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

711

1423

2134

2846

3557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.130

Hom.:

1878

Bravo

AF:

0.0984

Asia WGS

AF:

0.0550

AC:

193

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.1

(source)

DANN

Benign

0.85

PhyloP100

0.027

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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rs10519052

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