rs2918415

Variant summary

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

The NM_000176.3(NR3C1):​c.1184+34258T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,206 control chromosomes in the GnomAD database, including 1,807 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 0.15 ( 1807 hom., cov: 32)

Consequence

NR3C1
NM_000176.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164
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=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR3C1NM_000176.3 linkuse as main transcriptc.1184+34258T>G intron_variant ENST00000394464.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR3C1ENST00000394464.7 linkuse as main transcriptc.1184+34258T>G intron_variant 1 NM_000176.3 A1P04150-1

Frequencies

GnomAD3 genomes
AF:
0.147
AC:
22371
AN:
152088
Hom.:
1803
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.171
Gnomad AMI
AF:
0.240
Gnomad AMR
AF:
0.0819
Gnomad ASJ
AF:
0.0617
Gnomad EAS
AF:
0.0728
Gnomad SAS
AF:
0.0337
Gnomad FIN
AF:
0.205
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.156
Gnomad OTH
AF:
0.121
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.147
AC:
22405
AN:
152206
Hom.:
1807
Cov.:
32
AF XY:
0.145
AC XY:
10826
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.172
Gnomad4 AMR
AF:
0.0818
Gnomad4 ASJ
AF:
0.0617
Gnomad4 EAS
AF:
0.0728
Gnomad4 SAS
AF:
0.0327
Gnomad4 FIN
AF:
0.205
Gnomad4 NFE
AF:
0.156
Gnomad4 OTH
AF:
0.120
Alfa
AF:
0.144
Hom.:
1495
Bravo
AF:
0.140
Asia WGS
AF:
0.0740
AC:
257
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.8
DANN
Benign
0.75

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: rs2918415; hg19: chr5-142744963; API