rs6877893

Variant names:

• chr5-143347628-G-A
• rs6877893
• NM_000176.3:c.1185-33460C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-143347628-G-A
• chr5-143347628-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000176.3(NR3C1):​c.1185-33460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,928 control chromosomes in the GnomAD database, including 21,402 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 0.52 (21402 hom., cov: 32)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876
• Publications: 29 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 resistance

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.1185-33460C>T		intron_variant	Intron 2 of 8	ENST00000394464.7	NP_000167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000394464.7	c.1185-33460C>T		intron_variant	Intron 2 of 8	1	NM_000176.3	ENSP00000377977.2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79591 AN: 151810 Hom.: 21382 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.534

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79654 AN: 151928 Hom.: 21402 Cov.: 32 AF XY: 0.532 AC XY: 39482 AN XY: 74262

African (AFR) AF: 0.561 AC: 23255 AN: 41448

American (AMR) AF: 0.618 AC: 9442 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3468

East Asian (EAS) AF: 0.753 AC: 3891 AN: 5170

South Asian (SAS) AF: 0.609 AC: 2935 AN: 4818

European-Finnish (FIN) AF: 0.503 AC: 5296 AN: 10530

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31432 AN: 67906

Other (OTH) AF: 0.534 AC: 1125 AN: 2108

Alfa AF: 0.488 Hom.: 56755

Bravo AF: 0.534

Asia WGS AF: 0.633 AC: 2195 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	9.8
DANN	Benign	0.78
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6877893; hg19: chr5-142727193;