15-60499904-T-A
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_134261.3(RORA):c.1395A>T(p.Gly465Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,600,684 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00098 ( 11 hom. )
Consequence
RORA
NM_134261.3 synonymous
NM_134261.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.186
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 15-60499904-T-A is Benign according to our data. Variant chr15-60499904-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1675578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.186 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000977 (1415/1448426) while in subpopulation MID AF= 0.0225 (129/5722). AF 95% confidence interval is 0.0194. There are 11 homozygotes in gnomad4_exome. There are 762 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
High AC in GnomAd4 at 211 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RORA | NM_134261.3 | c.1395A>T | p.Gly465Gly | synonymous_variant | 10/11 | ENST00000335670.11 | NP_599023.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RORA | ENST00000335670.11 | c.1395A>T | p.Gly465Gly | synonymous_variant | 10/11 | 1 | NM_134261.3 | ENSP00000335087.6 |
Frequencies
GnomAD3 genomes AF: 0.00139 AC: 211AN: 152140Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00135 AC: 336AN: 248492Hom.: 3 AF XY: 0.00151 AC XY: 203AN XY: 134492
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GnomAD4 exome AF: 0.000977 AC: 1415AN: 1448426Hom.: 11 Cov.: 27 AF XY: 0.00106 AC XY: 762AN XY: 721554
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GnomAD4 genome AF: 0.00139 AC: 211AN: 152258Hom.: 1 Cov.: 32 AF XY: 0.00145 AC XY: 108AN XY: 74444
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | RORA: BP4, BP7, BS2; RORA-AS1: BS2 - |
RORA-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 19, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at