chr5-143412919-G-T

Variant names:

• chr5-143412919-G-T
• rs9324924
• ENST00000504572.5:c.-13-12067C>A

Variant summary

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

The NM_001364183.2(NR3C1):​c.-13-12067C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,958 control chromosomes in the GnomAD database, including 17,454 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 0.46 (17454 hom., cov: 32)
• Consequence: NR3C1 NM_001364183.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 23 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: Orphanet, Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000305502 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364183.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	NM_001364183.2		c.-13-12067C>A		intron	N/A	NP_001351112.1	P04150-3
	NR3C1	NM_001018074.1		c.-13-12067C>A		intron	N/A	NP_001018084.1	P04150-1
	NR3C1	NM_001018075.1		c.-13-12067C>A		intron	N/A	NP_001018085.1	P04150-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	ENST00000504572.5	TSL:1	c.-13-12067C>A		intron	N/A	ENSP00000422518.1	P04150-3
	NR3C1	ENST00000870492.1		c.-13-12067C>A		intron	N/A	ENSP00000540551.1
	NR3C1	ENST00000343796.6	TSL:5	c.-13-12067C>A		intron	N/A	ENSP00000343205.2	P04150-1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69122 AN: 151840 Hom.: 17420 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.455 AC: 69205 AN: 151958 Hom.: 17454 Cov.: 32 AF XY: 0.455 AC XY: 33770 AN XY: 74266

African (AFR) AF: 0.692 AC: 28657 AN: 41432

American (AMR) AF: 0.407 AC: 6218 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2051 AN: 5172

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4822

European-Finnish (FIN) AF: 0.420 AC: 4433 AN: 10550

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.350 AC: 23805 AN: 67948

Other (OTH) AF: 0.423 AC: 890 AN: 2104

Alfa AF: 0.388 Hom.: 17968

Bravo AF: 0.465

Asia WGS AF: 0.403 AC: 1400 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9324924; hg19: chr5-142792484;