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rs41423247

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000176.3(NR3C1):c.1184+646C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,026 control chromosomes in the GnomAD database, including 7,823 homozygotes. 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: 𝑓 0.31 ( 7823 hom., cov: 32)

Consequence

NR3C1
NM_000176.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.348
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR3C1NM_000176.3 linkuse as main transcriptc.1184+646C>G intron_variant ENST00000394464.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR3C1ENST00000394464.7 linkuse as main transcriptc.1184+646C>G intron_variant 1 NM_000176.3 A1P04150-1

Frequencies

GnomAD3 genomes
AF:
0.309
AC:
46918
AN:
151906
Hom.:
7819
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.219
Gnomad AMI
AF:
0.525
Gnomad AMR
AF:
0.257
Gnomad ASJ
AF:
0.244
Gnomad EAS
AF:
0.225
Gnomad SAS
AF:
0.226
Gnomad FIN
AF:
0.421
Gnomad MID
AF:
0.264
Gnomad NFE
AF:
0.372
Gnomad OTH
AF:
0.283
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.309
AC:
46951
AN:
152026
Hom.:
7823
Cov.:
32
AF XY:
0.306
AC XY:
22776
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.219
Gnomad4 AMR
AF:
0.256
Gnomad4 ASJ
AF:
0.244
Gnomad4 EAS
AF:
0.224
Gnomad4 SAS
AF:
0.224
Gnomad4 FIN
AF:
0.421
Gnomad4 NFE
AF:
0.372
Gnomad4 OTH
AF:
0.282
Alfa
AF:
0.339
Hom.:
1119
Bravo
AF:
0.295
Asia WGS
AF:
0.260
AC:
906
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
1.2
Dann
Benign
0.39

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: rs41423247; hg19: chr5-142778575; API