chr5-143325856-G-A

Variant names:

• chr5-143325856-G-A
• rs852982
• NM_000176.3:c.1185-11688C>T

Variant summary

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

The NM_000176.3(NR3C1):​c.1185-11688C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,940 control chromosomes in the GnomAD database, including 6,019 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 0.27 (6019 hom., cov: 32)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.1185-11688C>T		intron	N/A	NP_000167.1	P04150-1
	NR3C1	NM_001024094.2		c.1185-11688C>T		intron	N/A	NP_001019265.1	E5KQF6
	NR3C1	NM_001364183.2		c.1185-11688C>T		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.1185-11688C>T		intron	N/A	ENSP00000377977.2	P04150-1
	NR3C1	ENST00000231509.7	TSL:1	c.1185-11688C>T		intron	N/A	ENSP00000231509.3	P04150-3
	NR3C1	ENST00000504572.5	TSL:1	c.1185-11688C>T		intron	N/A	ENSP00000422518.1	P04150-3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41741 AN: 151822 Hom.: 6020 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.275 AC: 41766 AN: 151940 Hom.: 6019 Cov.: 32 AF XY: 0.269 AC XY: 19964 AN XY: 74244

African (AFR) AF: 0.257 AC: 10653 AN: 41410

American (AMR) AF: 0.196 AC: 2993 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3470

East Asian (EAS) AF: 0.0727 AC: 376 AN: 5172

South Asian (SAS) AF: 0.191 AC: 922 AN: 4822

European-Finnish (FIN) AF: 0.281 AC: 2956 AN: 10532

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21892 AN: 67948

Other (OTH) AF: 0.267 AC: 563 AN: 2110

Alfa AF: 0.301 Hom.: 8913

Bravo AF: 0.267

Asia WGS AF: 0.151 AC: 526 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.23
PhyloP100		-1.9
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: rs852982; hg19: chr5-142705421;