rs61753484
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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.1352-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 1,324,634 control chromosomes in the GnomAD database, including 53 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 0.0063 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0079 ( 49 hom. )
Consequence
NR3C1
NM_000176.3 intron
NM_000176.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.567
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=-0.87).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00628 (956/152254) while in subpopulation NFE AF= 0.00891 (606/68012). AF 95% confidence interval is 0.00832. There are 4 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR3C1 | NM_000176.3 | c.1352-46G>C | intron_variant | ENST00000394464.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR3C1 | ENST00000394464.7 | c.1352-46G>C | intron_variant | 1 | NM_000176.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00629 AC: 957AN: 152136Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00643 AC: 1555AN: 241952Hom.: 11 AF XY: 0.00664 AC XY: 874AN XY: 131548
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GnomAD4 exome AF: 0.00787 AC: 9231AN: 1172380Hom.: 49 Cov.: 15 AF XY: 0.00782 AC XY: 4669AN XY: 596974
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GnomAD4 genome ? AF: 0.00628 AC: 956AN: 152254Hom.: 4 Cov.: 32 AF XY: 0.00674 AC XY: 502AN XY: 74444
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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