rs5871845

Variant names:

• chr5-143404384-CGG-C
• rs5871845
• ENST00000503201.1:c.-24_-23delCC

Your query was ambiguous. Multiple possible variants found:

• chr5-143404384-CGG-C
• chr5-143404384-CGG-CG
• chr5-143404384-CGG-CGGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001364184.2(NR3C1):​c.-24_-23delCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000006 in 833,238 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: NR3C1 NM_001364184.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000006 (5/833238) while in subpopulation SAS AF= 0.000304 (5/16462). AF 95% confidence interval is 0.000119. There are 0 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C1	NM_001364184.2	c.-24_-23delCC		5_prime_UTR_variant	Exon 1 of 9		NP_001351113.1
NR3C1	NM_001018076.2	c.-24_-23delCC		5_prime_UTR_variant	Exon 1 of 9		NP_001018086.1
NR3C1	NM_001364183.2	c.-13-3534_-13-3533delCC		intron_variant	Intron 2 of 9		NP_001351112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000503201.1	c.-24_-23delCC		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000427672.1
NR3C1	ENST00000504572.5	c.-13-3534_-13-3533delCC		intron_variant	Intron 2 of 9	1		ENSP00000422518.1
NR3C1	ENST00000502892.5	c.-14+233_-14+234delCC		intron_variant	Intron 1 of 1	1		ENSP00000420856.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000600 AC: 5 AN: 833238 Hom.: 0 AF XY: 0.00000780 AC XY: 3 AN XY: 384820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000304

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5871845; hg19: chr5-142783949;