chr5-143378931-T-C

Position:

• chr5-143378931-T-C

Variant summary

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

The ENST00000394464.7(NR3C1):​c.1184+20725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,038 control chromosomes in the GnomAD database, including 51,365 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 0.82 (51365 hom., cov: 30)
• Consequence: NR3C1 ENST00000394464.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.1184+20725A>G		intron_variant		ENST00000394464.7	NP_000167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000394464.7	c.1184+20725A>G		intron_variant		1	NM_000176.3	ENSP00000377977	A1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124696 AN: 151920 Hom.: 51310 Cov.: 30

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.821 AC: 124811 AN: 152038 Hom.: 51365 Cov.: 30 AF XY: 0.822 AC XY: 61095 AN XY: 74308

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.822

Alfa AF: 0.792 Hom.: 60101

Bravo AF: 0.825

Asia WGS AF: 0.811 AC: 2818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.65

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: rs2963156; hg19: chr5-142758496;