rs3806855

Variant names:

• chr5-143404564-A-C
• rs3806855
• ENST00000504572.5:c.-13-3712T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-143404564-A-C
• chr5-143404564-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504572.5(NR3C1):​c.-13-3712T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 961,670 control chromosomes in the GnomAD database, including 11,938 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 (1747 hom., cov: 23)
  • Exomes 𝑓: 0.16 (10191 hom.)
• Consequence: NR3C1 ENST00000504572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• glucocorticoid resistance

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC128966704 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C1	NM_001364183.2	c.-13-3712T>G		intron_variant	Intron 2 of 9		NP_001351112.1
NR3C1	NM_001018074.1	c.-13-3712T>G		intron_variant	Intron 1 of 8		NP_001018084.1
NR3C1	NM_001018075.1	c.-13-3712T>G		intron_variant	Intron 1 of 8		NP_001018085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-13-3712T>G		intron_variant	Intron 2 of 9	1		ENSP00000422518.1
NR3C1	ENST00000502892.5	c.-14+55T>G		intron_variant	Intron 1 of 1	1		ENSP00000420856.1
NR3C1	ENST00000514699.1	c.-14+586T>G		intron_variant	Intron 1 of 1	1		ENSP00000426478.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 21568 AN: 143000 Hom.: 1744 Cov.: 23

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0232

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.156 AC: 127684 AN: 818580 Hom.: 10191 Cov.: 17 AF XY: 0.155 AC XY: 58797 AN XY: 378164

African (AFR) AF: 0.170 AC: 2632 AN: 15506

American (AMR) AF: 0.0813 AC: 79 AN: 972

Ashkenazi Jewish (ASJ) AF: 0.0636 AC: 325 AN: 5112

East Asian (EAS) AF: 0.0798 AC: 285 AN: 3572

South Asian (SAS) AF: 0.0328 AC: 534 AN: 16292

European-Finnish (FIN) AF: 0.199 AC: 53 AN: 266

Middle Eastern (MID) AF: 0.0281 AC: 45 AN: 1604

European-Non Finnish (NFE) AF: 0.160 AC: 120058 AN: 748450

Other (OTH) AF: 0.137 AC: 3673 AN: 26806

GnomAD4 genome AF: 0.151 AC: 21600 AN: 143090 Hom.: 1747 Cov.: 23 AF XY: 0.150 AC XY: 10395 AN XY: 69384

African (AFR) AF: 0.178 AC: 6848 AN: 38478

American (AMR) AF: 0.0859 AC: 1234 AN: 14364

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 216 AN: 3376

East Asian (EAS) AF: 0.0773 AC: 346 AN: 4478

South Asian (SAS) AF: 0.0364 AC: 156 AN: 4290

European-Finnish (FIN) AF: 0.216 AC: 1980 AN: 9176

Middle Eastern (MID) AF: 0.0214 AC: 6 AN: 280

European-Non Finnish (NFE) AF: 0.157 AC: 10356 AN: 65768

Other (OTH) AF: 0.122 AC: 245 AN: 2000

Alfa AF: 0.104 Hom.: 308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.43
PhyloP100		0.78
PromoterAI		-0.0072	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3806855; hg19: chr5-142784129;