5-143330421-C-T

Variant names:

• chr5-143330421-C-T
• rs33383
• NM_000176.3:c.1185-16253G>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.1185-16253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,946 control chromosomes in the GnomAD database, including 21,469 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 (21469 hom., cov: 33)
• Consequence: NR3C1 NM_000176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C1	NM_000176.3	c.1185-16253G>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.1185-16253G>A		intron_variant	Intron 2 of 8	1	NM_000176.3	ENSP00000377977.2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79710 AN: 151828 Hom.: 21450 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.525 AC: 79773 AN: 151946 Hom.: 21469 Cov.: 33 AF XY: 0.532 AC XY: 39522 AN XY: 74254

African (AFR) AF: 0.562 AC: 23306 AN: 41456

American (AMR) AF: 0.618 AC: 9446 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1820 AN: 3468

East Asian (EAS) AF: 0.752 AC: 3899 AN: 5182

South Asian (SAS) AF: 0.613 AC: 2953 AN: 4818

European-Finnish (FIN) AF: 0.503 AC: 5269 AN: 10484

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31479 AN: 67958

Other (OTH) AF: 0.536 AC: 1128 AN: 2106

Alfa AF: 0.483 Hom.: 20827

Bravo AF: 0.535

Asia WGS AF: 0.636 AC: 2203 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.36
PhyloP100		-1.3
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: rs33383; hg19: chr5-142709986;