rs852980

Variant names:

• chr5-143321291-G-C
• rs852980
• NM_000176.3:c.1185-7123C>G

Variant summary

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

The NM_000176.3(NR3C1):​c.1185-7123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,974 control chromosomes in the GnomAD database, including 21,534 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 0.53 (21534 hom., cov: 32)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 11 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]

RPL7P21 (HGNC:36762): (ribosomal protein L7 pseudogene 21)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

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.1185-7123C>G		intron	N/A	NP_000167.1	P04150-1
	NR3C1	NM_001024094.2		c.1185-7123C>G		intron	N/A	NP_001019265.1	E5KQF6
	NR3C1	NM_001364183.2		c.1185-7123C>G		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.1185-7123C>G		intron	N/A	ENSP00000377977.2	P04150-1
	NR3C1	ENST00000231509.7	TSL:1	c.1185-7123C>G		intron	N/A	ENSP00000231509.3	P04150-3
	NR3C1	ENST00000504572.5	TSL:1	c.1185-7123C>G		intron	N/A	ENSP00000422518.1	P04150-3

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79835 AN: 151856 Hom.: 21514 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.526 AC: 79898 AN: 151974 Hom.: 21534 Cov.: 32 AF XY: 0.533 AC XY: 39600 AN XY: 74294

African (AFR) AF: 0.563 AC: 23290 AN: 41404

American (AMR) AF: 0.619 AC: 9446 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1818 AN: 3466

East Asian (EAS) AF: 0.755 AC: 3914 AN: 5186

South Asian (SAS) AF: 0.614 AC: 2969 AN: 4834

European-Finnish (FIN) AF: 0.503 AC: 5313 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31542 AN: 67942

Other (OTH) AF: 0.535 AC: 1131 AN: 2114

Alfa AF: 0.500 Hom.: 2388

Bravo AF: 0.536

Asia WGS AF: 0.638 AC: 2216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.4
DANN	Benign	0.80
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs852980; hg19: chr5-142700856;