5-143413085-A-G

Position:

• chr5-143413085-A-G

Variant summary

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

The ENST00000504572.5(NR3C1):​c.-13-12233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,046 control chromosomes in the GnomAD database, including 14,514 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 0.43 (14514 hom., cov: 32)
• Consequence: NR3C1 ENST00000504572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_001018074.1	c.-13-12233T>C		intron_variant			NP_001018084.1
NR3C1	NM_001018075.1	c.-13-12233T>C		intron_variant			NP_001018085.1
NR3C1	NM_001018077.1	c.-13-12233T>C		intron_variant			NP_001018087.1
NR3C1	NM_001364183.2	c.-13-12233T>C		intron_variant			NP_001351112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-13-12233T>C		intron_variant		1		ENSP00000422518	P4
NR3C1	ENST00000343796.6	c.-13-12233T>C		intron_variant		5		ENSP00000343205	A1
NR3C1	ENST00000503701.1	n.353-3846T>C		intron_variant, non_coding_transcript_variant		3
NR3C1	ENST00000505058.5	n.242-3846T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65922 AN: 151928 Hom.: 14514 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.434 AC: 65952 AN: 152046 Hom.: 14514 Cov.: 32 AF XY: 0.436 AC XY: 32404 AN XY: 74328

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.424

Alfa AF: 0.416 Hom.: 17494

Bravo AF: 0.443

Asia WGS AF: 0.478 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7701443; hg19: chr5-142792650;