chr5-143404562-A-G

Position:

• chr5-143404562-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504572.5(NR3C1):​c.-13-3710T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 956,486 control chromosomes in the GnomAD database, including 11,975 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 0.16 (1745 hom., cov: 23)
  • Exomes 𝑓: 0.16 (10230 hom.)
• Consequence: NR3C1 ENST00000504572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR3C1	NM_001018074.1	c.-13-3710T>C		intron_variant
NR3C1	NM_001018075.1	c.-13-3710T>C		intron_variant
NR3C1	NM_001018077.1	c.-13-3710T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR3C1	ENST00000502892.5	c.-14+57T>C		intron_variant		1
NR3C1	ENST00000504572.5	c.-13-3710T>C		intron_variant		1		P4
NR3C1	ENST00000514699.1	c.-14+588T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 21522 AN: 136554 Hom.: 1742 Cov.: 23

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.0650

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.0238

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.156 AC: 128102 AN: 819840 Hom.: 10230 Cov.: 17 AF XY: 0.156 AC XY: 58992 AN XY: 378782

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0813

Gnomad4 ASJ exome AF: 0.0637

Gnomad4 EAS exome AF: 0.0799

Gnomad4 SAS exome AF: 0.0326

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.158 AC: 21554 AN: 136646 Hom.: 1745 Cov.: 23 AF XY: 0.158 AC XY: 10379 AN XY: 65660

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0650

Gnomad4 EAS AF: 0.0869

Gnomad4 SAS AF: 0.0409

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0595 Hom.: 63

Asia WGS AF: 0.0670 AC: 228 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3806854; hg19: chr5-142784127;