chr5-143403703-A-G

Position:

• chr5-143403703-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001364183.2(NR3C1):​c.-13-2851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 983,372 control chromosomes in the GnomAD database, including 11 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 0.0038 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (9 hom.)
• Consequence: NR3C1 NM_001364183.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00377 (567/150546) while in subpopulation NFE AF= 0.0056 (380/67822). AF 95% confidence interval is 0.00514. There are 2 homozygotes in gnomad4. There are 270 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.-506T>C		upstream_gene_variant		ENST00000394464.7	NP_000167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000394464.7	c.-506T>C		upstream_gene_variant		1	NM_000176.3	ENSP00000377977.2

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 567 AN: 150442 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00122

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00193

GnomAD4 exome AF: 0.00522 AC: 4349 AN: 832826 Hom.: 9 Cov.: 32 AF XY: 0.00530 AC XY: 2040 AN XY: 384650

Gnomad4 AFR exome AF: 0.000587

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.000388

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000607

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.00557

Gnomad4 OTH exome AF: 0.00305

GnomAD4 genome AF: 0.00377 AC: 567 AN: 150546 Hom.: 2 Cov.: 33 AF XY: 0.00367 AC XY: 270 AN XY: 73622

Gnomad4 AFR AF: 0.00122

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.000578

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.00560

Gnomad4 OTH AF: 0.00191

Alfa AF: 0.00427 Hom.: 0

Bravo AF: 0.00297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10482606; hg19: chr5-142783268;