GeneBe

5-143404384-CGG-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000503201.1(NR3C1):​c.-24_-23delCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000006 in 833,238 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

NR3C1
ENST00000503201.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

Publications

9 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: Benign. The variant received -8 ACMG points.

BS1
Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000006 (5/833238) while in subpopulation SAS AF = 0.000304 (5/16462). AF 95% confidence interval is 0.000119. There are 0 homozygotes in GnomAdExome4. There are 3 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR3C1NR_157096.2 linkn.97_98delCC non_coding_transcript_exon_variant Exon 1 of 8
NR3C1NM_001364184.2 linkc.-24_-23delCC 5_prime_UTR_variant Exon 1 of 9 NP_001351113.1
NR3C1NM_001018076.2 linkc.-24_-23delCC 5_prime_UTR_variant Exon 1 of 9 NP_001018086.1 P04150-1F1D8N4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR3C1ENST00000503201.1 linkc.-24_-23delCC 5_prime_UTR_variant Exon 1 of 9 1 ENSP00000427672.1 P04150-1
NR3C1ENST00000504572.5 linkc.-13-3534_-13-3533delCC intron_variant Intron 2 of 9 1 ENSP00000422518.1 P04150-3
NR3C1ENST00000502892.5 linkc.-14+233_-14+234delCC intron_variant Intron 1 of 1 1 ENSP00000420856.1 Q3MSN4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000600
AC:
5
AN:
833238
Hom.:
0
AF XY:
0.00000780
AC XY:
3
AN XY:
384820
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
15788
American (AMR)
AF:
0.00
AC:
0
AN:
984
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
5154
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3632
South Asian (SAS)
AF:
0.000304
AC:
5
AN:
16462
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
276
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1620
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
762018
Other (OTH)
AF:
0.00
AC:
0
AN:
27304
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
6
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.65

Splicing

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

Publications

Other links and lift over

dbSNP: rs5871845; hg19: chr5-142783949; API