rs6196
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000176.3(NR3C1):āc.2298T>Cā(p.Asn766=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,080 control chromosomes in the GnomAD database, including 19,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.15 ( 1921 hom., cov: 31)
Exomes š: 0.15 ( 17969 hom. )
Consequence
NR3C1
NM_000176.3 synonymous
NM_000176.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.67
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 5-143281925-A-G is Benign according to our data. Variant chr5-143281925-A-G is described in ClinVar as [Benign]. Clinvar id is 351364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-143281925-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.67 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR3C1 | NM_000176.3 | c.2298T>C | p.Asn766= | synonymous_variant | 9/9 | ENST00000394464.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR3C1 | ENST00000394464.7 | c.2298T>C | p.Asn766= | synonymous_variant | 9/9 | 1 | NM_000176.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.152 AC: 23036AN: 152052Hom.: 1917 Cov.: 31
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GnomAD3 exomes AF: 0.124 AC: 31150AN: 250760Hom.: 2496 AF XY: 0.121 AC XY: 16454AN XY: 135596
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GnomAD4 exome AF: 0.150 AC: 219156AN: 1460910Hom.: 17969 Cov.: 31 AF XY: 0.146 AC XY: 105980AN XY: 726802
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GnomAD4 genome ? AF: 0.152 AC: 23070AN: 152170Hom.: 1921 Cov.: 31 AF XY: 0.150 AC XY: 11138AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glucocorticoid resistance Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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