dbSNP rs10431796: RORA:c.197-24720C>T (chr15-60556571-G-A) – 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.197-24720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,012 control chromosomes in the GnomAD database, including 12,091 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 0.38 ( 12091 hom., cov: 32)

Consequence

RORA
NM_134261.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.33

Publications

3 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

new If you want to explore the variant's impact on the transcript NM_134261.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RORA	NM_134261.3	MANE Select	c.197-24720C>T	intron	N/A	NP_599023.1	P35398-2
RORA	NM_134260.3		c.295+282C>T	intron	N/A	NP_599022.1	P35398-1
RORA	NM_002943.4		c.272-24720C>T	intron	N/A	NP_002934.1	A0A0C4DFP5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RORA	ENST00000335670.11	TSL:1 MANE Select	c.197-24720C>T	intron	N/A	ENSP00000335087.6	P35398-2
RORA	ENST00000261523.9	TSL:1	c.295+282C>T	intron	N/A	ENSP00000261523.5	P35398-1
RORA	ENST00000309157.8	TSL:1	c.272-24720C>T	intron	N/A	ENSP00000309753.3	A0A0C4DFP5

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57568

AN:

151894

Hom.:

12085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.379

AC:

57584

AN:

152012

Hom.:

12091

Cov.:

AF XY:

0.387

AC XY:

28767

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.202

AC:

8359

AN:

41468

American (AMR)

AF:

0.404

AC:

6170

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1298

AN:

3470

East Asian (EAS)

AF:

0.746

AC:

3863

AN:

5178

South Asian (SAS)

AF:

0.484

AC:

2328

AN:

4814

European-Finnish (FIN)

AF:

0.534

AC:

5639

AN:

10556

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28571

AN:

67926

Other (OTH)

AF:

0.366

AC:

773

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1729

3458

5187

6916

8645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.404

Hom.:

54820

Bravo

AF:

0.356

Asia WGS

AF:

0.591

AC:

2054

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.039

(source)

DANN

Benign

0.22

PhyloP100

-3.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over