rs17209258
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000176.3(NR3C1):c.2023+1628T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 926,686 control chromosomes in the GnomAD database, including 18,718 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 0.16 ( 2398 hom., cov: 31)
Exomes 𝑓: 0.20 ( 16320 hom. )
Consequence
NR3C1
NM_000176.3 intron
NM_000176.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.399
Genes affected
NR3C1 (HGNC:7978): (nuclear receptor subfamily 3 group C member 1) This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175). [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR3C1 | NM_000176.3 | c.2023+1628T>C | intron_variant | ENST00000394464.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR3C1 | ENST00000394464.7 | c.2023+1628T>C | intron_variant | 1 | NM_000176.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.162 AC: 24513AN: 151480Hom.: 2397 Cov.: 31
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GnomAD4 exome AF: 0.202 AC: 156921AN: 775104Hom.: 16320 Cov.: 12 AF XY: 0.203 AC XY: 72836AN XY: 359266
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GnomAD4 genome ? AF: 0.162 AC: 24515AN: 151582Hom.: 2398 Cov.: 31 AF XY: 0.162 AC XY: 11973AN XY: 74056
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at