5-143412919-G-T

Position:

• chr5-143412919-G-T

Variant summary

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

The NM_001364183.2(NR3C1):​c.-13-12067C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,958 control chromosomes in the GnomAD database, including 17,454 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 0.46 (17454 hom., cov: 32)
• Consequence: NR3C1 NM_001364183.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

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]

NR3C1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_001364183.2	c.-13-12067C>A		intron_variant			NP_001351112.1
NR3C1	NM_001018074.1	c.-13-12067C>A		intron_variant			NP_001018084.1
NR3C1	NM_001018075.1	c.-13-12067C>A		intron_variant			NP_001018085.1
NR3C1	NM_001018077.1	c.-13-12067C>A		intron_variant			NP_001018087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-13-12067C>A		intron_variant		1		ENSP00000422518.1
NR3C1	ENST00000343796.6	c.-13-12067C>A		intron_variant		5		ENSP00000343205.2
NR3C1	ENST00000503701.1	n.353-3680C>A		intron_variant		3
NR3C1	ENST00000505058.5	n.242-3680C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69122 AN: 151840 Hom.: 17420 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 69205 AN: 151958 Hom.: 17454 Cov.: 32 AF XY: 0.455 AC XY: 33770 AN XY: 74266

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.423

Alfa AF: 0.373 Hom.: 11231

Bravo AF: 0.465

Asia WGS AF: 0.403 AC: 1400 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
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: rs9324924; hg19: chr5-142792484;