chr5-143282800-G-GAT

Position:

• chr5-143282800-G-GAT

Variant summary

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

The NM_000176.3(NR3C1):​c.2024-76_2024-75insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000561 in 1,407,738 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000069 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000055 (1 hom.)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 amr. gnomad4 allele frequency = 0.0000686 (10/145814) while in subpopulation AMR AF= 0.000345 (5/14474). AF 95% confidence interval is 0.000135. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.2024-76_2024-75insAT		intron_variant		ENST00000394464.7	NP_000167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000394464.7	c.2024-76_2024-75insAT		intron_variant		1	NM_000176.3	ENSP00000377977	A1

Frequencies

GnomAD3 genomes AF: 0.0000686 AC: 10 AN: 145814 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000345

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000547 AC: 69 AN: 1261924 Hom.: 1 AF XY: 0.0000537 AC XY: 34 AN XY: 633426

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000264

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000686 AC: 10 AN: 145814 Hom.: 0 Cov.: 30 AF XY: 0.0000425 AC XY: 3 AN XY: 70648

Gnomad4 AFR AF: 0.000128

Gnomad4 AMR AF: 0.000345

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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: rs10482703; hg19: chr5-142662365;