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GeneBe

rs6198

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_000176.3(NR3C1):c.*3833A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,190 control chromosomes in the GnomAD database, including 1,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1343 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

NR3C1
NM_000176.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 5-143278056-T-C is Benign according to our data. Variant chr5-143278056-T-C is described in ClinVar as [Benign]. Clinvar id is 351314.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR3C1NM_000176.3 linkuse as main transcriptc.*3833A>G 3_prime_UTR_variant 9/9 ENST00000394464.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR3C1ENST00000394464.7 linkuse as main transcriptc.*3833A>G 3_prime_UTR_variant 9/91 NM_000176.3 A1P04150-1
NR3C1ENST00000415690.6 linkuse as main transcriptc.*1308A>G 3_prime_UTR_variant 9/91 P04150-2
NR3C1ENST00000343796.6 linkuse as main transcriptc.*3833A>G 3_prime_UTR_variant 9/95 A1P04150-1

Frequencies

GnomAD3 genomes
AF:
0.117
AC:
17741
AN:
152072
Hom.:
1349
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0468
Gnomad AMI
AF:
0.0888
Gnomad AMR
AF:
0.108
Gnomad ASJ
AF:
0.231
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.157
Gnomad FIN
AF:
0.0778
Gnomad MID
AF:
0.291
Gnomad NFE
AF:
0.166
Gnomad OTH
AF:
0.137
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.116
AC:
17729
AN:
152190
Hom.:
1343
Cov.:
32
AF XY:
0.113
AC XY:
8398
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0467
Gnomad4 AMR
AF:
0.108
Gnomad4 ASJ
AF:
0.231
Gnomad4 EAS
AF:
0.00173
Gnomad4 SAS
AF:
0.157
Gnomad4 FIN
AF:
0.0778
Gnomad4 NFE
AF:
0.166
Gnomad4 OTH
AF:
0.136
Alfa
AF:
0.161
Hom.:
3545
Bravo
AF:
0.114
Asia WGS
AF:
0.0740
AC:
258
AN:
3470

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Glucocorticoid resistance Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
15
Dann
Benign
0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6198; hg19: chr5-142657621; API