5-143405048-C-T

Position:

• chr5-143405048-C-T

Variant summary

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

The NM_001364183.2(NR3C1):​c.-13-4196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 868,340 control chromosomes in the GnomAD database, including 71 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 0.010 (21 hom., cov: 31)
  • Exomes 𝑓: 0.0080 (50 hom.)
• Consequence: NR3C1 NM_001364183.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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]

LOC128966704 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0104 (1577/152316) while in subpopulation SAS AF= 0.036 (174/4828). AF 95% confidence interval is 0.0317. There are 21 homozygotes in gnomad4. There are 833 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_001364183.2	c.-13-4196G>A		intron_variant			NP_001351112.1
NR3C1	NM_001018074.1	c.-13-4196G>A		intron_variant			NP_001018084.1
NR3C1	NM_001018075.1	c.-13-4196G>A		intron_variant			NP_001018085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-13-4196G>A		intron_variant		1		ENSP00000422518.1
NR3C1	ENST00000514699.1	c.-14+102G>A		intron_variant		1		ENSP00000426478.1
NR3C1	ENST00000343796.6	c.-13-4196G>A		intron_variant		5		ENSP00000343205.2

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1573 AN: 152198 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00851

Gnomad OTH AF: 0.0181

GnomAD4 exome AF: 0.00798 AC: 5713 AN: 716024 Hom.: 50 AF XY: 0.00827 AC XY: 2750 AN XY: 332618

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00489

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.00794

Gnomad4 NFE exome AF: 0.00673

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0104 AC: 1577 AN: 152316 Hom.: 21 Cov.: 31 AF XY: 0.0112 AC XY: 833 AN XY: 74468

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.00851

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00379 Hom.: 0

Bravo AF: 0.00997

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.6
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10482603; hg19: chr5-142784613;