5-143320934-C-T

Variant names:

• chr5-143320934-C-T
• rs33389
• NM_000176.3:c.1185-6766G>A

Variant summary

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

The NM_000176.3(NR3C1):​c.1185-6766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,032 control chromosomes in the GnomAD database, including 1,609 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 0.14 (1609 hom., cov: 32)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 37 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.1185-6766G>A		intron_variant	Intron 2 of 8	ENST00000394464.7	NP_000167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000394464.7	c.1185-6766G>A		intron_variant	Intron 2 of 8	1	NM_000176.3	ENSP00000377977.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21031 AN: 151914 Hom.: 1609 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.138 AC: 21045 AN: 152032 Hom.: 1609 Cov.: 32 AF XY: 0.136 AC XY: 10134 AN XY: 74314

African (AFR) AF: 0.141 AC: 5846 AN: 41452

American (AMR) AF: 0.0806 AC: 1231 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0623 AC: 216 AN: 3468

East Asian (EAS) AF: 0.0717 AC: 372 AN: 5186

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4810

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10552

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10614 AN: 67974

Other (OTH) AF: 0.113 AC: 239 AN: 2108

Alfa AF: 0.134 Hom.: 2094

Bravo AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.66
DANN	Benign	0.45
PhyloP100		-0.28
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: rs33389; hg19: chr5-142700499;