rs340020

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_134261.3(RORA):​c.196+64767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 151,606 control chromosomes in the GnomAD database, including 11 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 0.0069 ( 11 hom., cov: 30)

Consequence

RORA
NM_134261.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27
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-AS1 (HGNC:51410): (RORA antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00689 (1045/151606) while in subpopulation AFR AF= 0.0242 (998/41232). AF 95% confidence interval is 0.023. There are 11 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1045 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RORANM_134261.3 linkuse as main transcriptc.196+64767G>A intron_variant ENST00000335670.11
RORA-AS1NR_120342.1 linkuse as main transcriptn.567+12833C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RORAENST00000335670.11 linkuse as main transcriptc.196+64767G>A intron_variant 1 NM_134261.3 P35398-2
RORA-AS1ENST00000559824.5 linkuse as main transcriptn.567+12833C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00692
AC:
1048
AN:
151494
Hom.:
11
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00204
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00528
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00689
AC:
1045
AN:
151606
Hom.:
11
Cov.:
30
AF XY:
0.00667
AC XY:
494
AN XY:
74100
show subpopulations
Gnomad4 AFR
AF:
0.0242
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00523
Alfa
AF:
0.00365
Hom.:
0
Bravo
AF:
0.00791
Asia WGS
AF:
0.000578
AC:
2
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.63
DANN
Benign
0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs340020; hg19: chr15-60906089; API