Genetic Variant RORA:c.167-50162C>T (chr15-60728848-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.167-50162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 152,198 control chromosomes in the GnomAD database, including 52 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 0.0070 ( 52 hom., cov: 32)

Consequence

RORA
NM_134261.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0450

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder with or without epilepsy or cerebellar ataxia
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

RORA 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3 link	c.167-50162C>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1	P35398-2
RORA	XM_047432928.1 link	c.-1751-50162C>T		intron_variant	Intron 1 of 10		XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11 link	c.167-50162C>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6		P35398-2

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00861

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

GnomAD4 genome

AF:

0.00696

AC:

1059

AN:

152198

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

592

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41530

American (AMR)

AF:

0.0112

AC:

171

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.145

AC:

751

AN:

5168

South Asian (SAS)

AF:

0.00685

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000661

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68010

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00309

Hom.:

Bravo

AF:

0.00887

Asia WGS

AF:

0.0700

AC:

244

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

(source)

DANN

Benign

0.76

PhyloP100

-0.045

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over