rs10482604

chr5-143404037-T-C

Variant summary

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

The ENST00000504572.5(NR3C1):c.-13-3185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 985,386 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 0.0054 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (6 hom.)
• Consequence: NR3C1 ENST00000504572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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=-0.77).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00536 (814/151918) while in subpopulation EAS AF= 0.0223 (114/5120). AF 95% confidence interval is 0.0189. There are 5 homozygotes in gnomad4. There are 409 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR3C1	NM_001364181.2	c.-65A>G		5_prime_UTR_variant	1/9
NR3C1	NM_001018074.1	c.-13-3185A>G		intron_variant
NR3C1	NM_001018075.1	c.-13-3185A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR3C1	ENST00000502892.5	c.-14+582A>G		intron_variant		1
NR3C1	ENST00000503201.1	c.-14+339A>G		intron_variant		1		A1
NR3C1	ENST00000504572.5	c.-13-3185A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.00531 AC: 806 AN: 151810 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000605 AC: 504 AN: 833468 Hom.: 6 Cov.: 32 AF XY: 0.000561 AC XY: 216 AN XY: 384974

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0297

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000446

Gnomad4 OTH exome AF: 0.00355

GnomAD4 genome AF: 0.00536 AC: 814 AN: 151918 Hom.: 5 Cov.: 32 AF XY: 0.00551 AC XY: 409 AN XY: 74248

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0223

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.00569

Asia WGS AF: 0.0170 AC: 58 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	11
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10482604; hg19: chr5-142783602;