rs2307674

Variant names:

• chr5-143296616-AAACAAC-A
• rs2307674
• NM_000176.3:c.1893-1032_1893-1027delGTTGTT

Your query was ambiguous. Multiple possible variants found:

• chr5-143296616-AAACAAC-A
• chr5-143296616-AAACAAC-AAAC
• chr5-143296616-AAACAAC-AAACAACAAC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000176.3(NR3C1):​c.1893-1032_1893-1027delGTTGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,992 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 28)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 1 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: Orphanet, Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000300303 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000176.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	NM_000176.3	MANE Select	c.1893-1032_1893-1027delGTTGTT		intron	N/A	NP_000167.1	P04150-1
	NR3C1	NM_001024094.2		c.1896-1032_1896-1027delGTTGTT		intron	N/A	NP_001019265.1	E5KQF6
	NR3C1	NM_001364183.2		c.1896-1032_1896-1027delGTTGTT		intron	N/A	NP_001351112.1	P04150-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	ENST00000394464.7	TSL:1 MANE Select	c.1893-1032_1893-1027delGTTGTT		intron	N/A	ENSP00000377977.2	P04150-1
	NR3C1	ENST00000231509.7	TSL:1	c.1896-1032_1896-1027delGTTGTT		intron	N/A	ENSP00000231509.3	P04150-3
	NR3C1	ENST00000504572.5	TSL:1	c.1896-1032_1896-1027delGTTGTT		intron	N/A	ENSP00000422518.1	P04150-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151992 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151992 Hom.: 0 Cov.: 28 AF XY: 0.0000269 AC XY: 2 AN XY: 74234

African (AFR) AF: 0.00 AC: 0 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 63

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs2307674; hg19: chr5-142676181;