chr5-143296616-AAAC-A

Position:

• chr5-143296616-AAAC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000176.3(NR3C1):​c.1893-1029_1893-1027del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,060 control chromosomes in the GnomAD database, including 1,759 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1759 hom., cov: 28)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.1893-1029_1893-1027del		intron_variant		ENST00000394464.7	NP_000167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000394464.7	c.1893-1029_1893-1027del		intron_variant		1	NM_000176.3	ENSP00000377977	A1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21990 AN: 151944 Hom.: 1755 Cov.: 28

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.145 AC: 22018 AN: 152060 Hom.: 1759 Cov.: 28 AF XY: 0.143 AC XY: 10619 AN XY: 74332

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0811

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.0709

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.116

Bravo AF: 0.137

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs2307674; hg19: chr5-142676181;