rs10052957

Positions:

• chr5-143407136-G-A

Variant summary

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

The NM_001364183.2(NR3C1):​c.-13-6284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,140 control chromosomes in the GnomAD database, including 6,254 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 0.28 (6250 hom., cov: 32)
  • Exomes 𝑓: 0.30 (4 hom.)
• Consequence: NR3C1 NM_001364183.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC128966704	XM_054328421.1	c.-1495C>T		5_prime_UTR_premature_start_codon_gain_variant	1/2		XP_054184396.1
LOC128966704	XM_054328421.1	c.-1495C>T		5_prime_UTR_variant	1/2		XP_054184396.1
NR3C1	NM_001364183.2	c.-13-6284C>T		intron_variant			NP_001351112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-13-6284C>T		intron_variant		1		ENSP00000422518.1
NR3C1	ENST00000343796.6	c.-13-6284C>T		intron_variant		5		ENSP00000343205.2
ENSG00000279130	ENST00000623204.1	n.178G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42654 AN: 151968 Hom.: 6248 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.304 AC: 17 AN: 56 Hom.: 4 Cov.: 0 AF XY: 0.250 AC XY: 9 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.281 AC: 42685 AN: 152084 Hom.: 6250 Cov.: 32 AF XY: 0.275 AC XY: 20418 AN XY: 74350

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.0946

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.279

Alfa AF: 0.308 Hom.: 9695

Bravo AF: 0.273

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10052957; hg19: chr5-142786701;