ENST00000503201.1:c.-24_-23delCC
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
ENST00000503201.1 5_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.646
Publications
9 publications found
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 resistanceInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
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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 |
---|---|---|---|---|---|---|---|---|
NR3C1 | NR_157096.2 | n.97_98delCC | non_coding_transcript_exon_variant | Exon 1 of 8 | ||||
NR3C1 | NM_001364184.2 | c.-24_-23delCC | 5_prime_UTR_variant | Exon 1 of 9 | NP_001351113.1 | |||
NR3C1 | NM_001018076.2 | c.-24_-23delCC | 5_prime_UTR_variant | Exon 1 of 9 | NP_001018086.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NR3C1 | ENST00000503201.1 | c.-24_-23delCC | 5_prime_UTR_variant | Exon 1 of 9 | 1 | ENSP00000427672.1 | ||||
NR3C1 | ENST00000504572.5 | c.-13-3534_-13-3533delCC | intron_variant | Intron 2 of 9 | 1 | ENSP00000422518.1 | ||||
NR3C1 | ENST00000502892.5 | c.-14+233_-14+234delCC | intron_variant | Intron 1 of 1 | 1 | ENSP00000420856.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000600 AC: 5AN: 833238Hom.: 0 AF XY: 0.00000780 AC XY: 3AN XY: 384820 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
833238
Hom.:
AF XY:
AC XY:
3
AN XY:
384820
show subpopulations
African (AFR)
AF:
AC:
0
AN:
15788
American (AMR)
AF:
AC:
0
AN:
984
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
5154
East Asian (EAS)
AF:
AC:
0
AN:
3632
South Asian (SAS)
AF:
AC:
5
AN:
16462
European-Finnish (FIN)
AF:
AC:
0
AN:
276
Middle Eastern (MID)
AF:
AC:
0
AN:
1620
European-Non Finnish (NFE)
AF:
AC:
0
AN:
762018
Other (OTH)
AF:
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
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10
<30
30-35
35-40
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>80
Age
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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