chr5-143362972-T-C

Position:

• chr5-143362972-T-C

Variant summary

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

The NM_000176.3(NR3C1):​c.1184+36684A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,138 control chromosomes in the GnomAD database, including 1,806 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 0.15 (1806 hom., cov: 31)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR3C1	NM_000176.3	c.1184+36684A>G		intron_variant		ENST00000394464.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR3C1	ENST00000394464.7	c.1184+36684A>G		intron_variant		1	NM_000176.3	A1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22316 AN: 152020 Hom.: 1802 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.147 AC: 22350 AN: 152138 Hom.: 1806 Cov.: 31 AF XY: 0.145 AC XY: 10777 AN XY: 74344

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0820

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.0720

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.119

Alfa AF: 0.140 Hom.: 2083

Bravo AF: 0.140

Asia WGS AF: 0.0740 AC: 257 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	1.5
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2963154; hg19: chr5-142742537;