rs9324923
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000176.3(NR3C1):c.-14+744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 399,424 control chromosomes in the GnomAD database, including 3 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 0.0043 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 1 hom. )
Consequence
NR3C1
NM_000176.3 intron
NM_000176.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.00300
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=-0.79).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00428 (652/152328) while in subpopulation AFR AF= 0.015 (622/41566). AF 95% confidence interval is 0.014. There are 2 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR3C1 | NM_000176.3 | c.-14+744C>T | intron_variant | ENST00000394464.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR3C1 | ENST00000394464.7 | c.-14+744C>T | intron_variant | 1 | NM_000176.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00425 AC: 647AN: 152210Hom.: 2 Cov.: 33
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GnomAD4 exome AF: 0.000320 AC: 79AN: 247096Hom.: 1 AF XY: 0.000292 AC XY: 34AN XY: 116414
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GnomAD4 genome ? AF: 0.00428 AC: 652AN: 152328Hom.: 2 Cov.: 33 AF XY: 0.00427 AC XY: 318AN XY: 74484
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ClinVar
Not reported inComputational scores
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Name
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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