ENST00000504572.5:c.-13-11260A>G

Variant names:

• chr5-143412112-T-C
• rs11749561
• ENST00000504572.5:c.-13-11260A>G

Variant summary

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

The ENST00000504572.5(NR3C1):​c.-13-11260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,828 control chromosomes in the GnomAD database, including 16,858 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 (16858 hom., cov: 30)
• Consequence: NR3C1 ENST00000504572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• Publications: 8 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

ENSG00000305502 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504572.5. 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.-13-11260A>G		intron	N/A	NP_001351112.1
	NR3C1	NM_001018074.1		c.-13-11260A>G		intron	N/A	NP_001018084.1
	NR3C1	NM_001018075.1		c.-13-11260A>G		intron	N/A	NP_001018085.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	ENST00000504572.5	TSL:1	c.-13-11260A>G		intron	N/A	ENSP00000422518.1
	NR3C1	ENST00000870492.1		c.-13-11260A>G		intron	N/A	ENSP00000540551.1
	NR3C1	ENST00000343796.6	TSL:5	c.-13-11260A>G		intron	N/A	ENSP00000343205.2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69428 AN: 151708 Hom.: 16863 Cov.: 30

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.457 AC: 69445 AN: 151828 Hom.: 16858 Cov.: 30 AF XY: 0.452 AC XY: 33530 AN XY: 74182

African (AFR) AF: 0.364 AC: 15081 AN: 41390

American (AMR) AF: 0.397 AC: 6058 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1581 AN: 3472

East Asian (EAS) AF: 0.103 AC: 530 AN: 5158

South Asian (SAS) AF: 0.320 AC: 1535 AN: 4800

European-Finnish (FIN) AF: 0.549 AC: 5778 AN: 10516

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37178 AN: 67922

Other (OTH) AF: 0.469 AC: 990 AN: 2110

Alfa AF: 0.506 Hom.: 35947

Bravo AF: 0.439

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.78
PhyloP100		-0.65
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: rs11749561; hg19: chr5-142791677;