5-143404384-CGG-CGGG

Variant names:

• chr5-143404384-C-CG
• rs5871845
• ENST00000503201.1:c.-23dupC

Variant summary

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

The NM_001364184.2(NR3C1):​c.-23dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 985,276 control chromosomes in the GnomAD database, including 2,059 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (444 hom., cov: 31)
  • Exomes 𝑓: 0.059 (1615 hom.)
• Consequence: NR3C1 NM_001364184.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C1	NM_001364184.2	c.-23dupC		5_prime_UTR_variant	Exon 1 of 9		NP_001351113.1
NR3C1	NM_001018076.2	c.-23dupC		5_prime_UTR_variant	Exon 1 of 9		NP_001018086.1
NR3C1	NM_001364183.2	c.-13-3533dupC		intron_variant	Intron 2 of 9		NP_001351112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000503201.1	c.-23dupC		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000427672.1
NR3C1	ENST00000504572.5	c.-13-3533dupC		intron_variant	Intron 2 of 9	1		ENSP00000422518.1
NR3C1	ENST00000502892.5	c.-14+234dupC		intron_variant	Intron 1 of 1	1		ENSP00000420856.1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9619 AN: 151946 Hom.: 442 Cov.: 31

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0589 AC: 49050 AN: 833220 Hom.: 1615 Cov.: 32 AF XY: 0.0585 AC XY: 22504 AN XY: 384810

Gnomad4 AFR exome AF: 0.0564

Gnomad4 AMR exome AF: 0.0447

Gnomad4 ASJ exome AF: 0.0345

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0559

Gnomad4 OTH exome AF: 0.0717

GnomAD4 genome AF: 0.0633 AC: 9627 AN: 152056 Hom.: 444 Cov.: 31 AF XY: 0.0652 AC XY: 4844 AN XY: 74346

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.0539

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0455

Gnomad4 NFE AF: 0.0559

Gnomad4 OTH AF: 0.0634

Bravo AF: 0.0602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5871845; hg19: chr5-142783949;