GeneBe

rs10482612

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000176.3(NR3C1):​c.-219C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

NR3C1
NM_000176.3 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

4 publications found
Variant links:
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]
NR3C1 Gene-Disease associations (from GenCC):
  • glucocorticoid resistance
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000176.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NR3C1
NM_000176.3
MANE Select
c.-219C>T
5_prime_UTR_premature_start_codon_gain
Exon 1 of 9NP_000167.1
NR3C1
NM_000176.3
MANE Select
c.-219C>T
5_prime_UTR
Exon 1 of 9NP_000167.1
NR3C1
NM_001024094.2
c.-219C>T
5_prime_UTR_premature_start_codon_gain
Exon 1 of 9NP_001019265.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NR3C1
ENST00000394464.7
TSL:1 MANE Select
c.-219C>T
5_prime_UTR_premature_start_codon_gain
Exon 1 of 9ENSP00000377977.2
NR3C1
ENST00000231509.7
TSL:1
c.-219C>T
5_prime_UTR_premature_start_codon_gain
Exon 1 of 9ENSP00000231509.3
NR3C1
ENST00000394464.7
TSL:1 MANE Select
c.-219C>T
5_prime_UTR
Exon 1 of 9ENSP00000377977.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
1
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
11
DANN
Benign
0.93
PhyloP100
-0.086
PromoterAI
0.020
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs10482612; hg19: chr5-142782981; API