rs10482610

Variant names:

• chr5-143403450-G-GC
• rs10482610
• NM_000176.3:c.-254_-253insG

Your query was ambiguous. Multiple possible variants found:

• chr5-143403450-G-GC
• chr5-143403450-G-GGCC
• chr5-143403450-G-GGGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000176.3(NR3C1):​c.-254_-253insG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.98 (73267 hom., cov: 0)
  • Exomes 𝑓: 1.0 (415430 hom.)
• Consequence: NR3C1 NM_000176.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 2 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]

NR3C1 Gene-Disease associations (from GenCC):

• glucocorticoid resistance

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	NM_000176.3	MANE Select	c.-254_-253insG		5_prime_UTR	Exon 1 of 9	NP_000167.1
	NR3C1	NM_001024094.2		c.-254_-253insG		5_prime_UTR	Exon 1 of 9	NP_001019265.1
	NR3C1	NM_001204258.2		c.-332_-331insG		5_prime_UTR	Exon 1 of 9	NP_001191187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C1	ENST00000394464.7	TSL:1 MANE Select	c.-254_-253insG		5_prime_UTR	Exon 1 of 9	ENSP00000377977.2
	NR3C1	ENST00000231509.7	TSL:1	c.-254_-253insG		5_prime_UTR	Exon 1 of 9	ENSP00000231509.3
	NR3C1	ENST00000504572.5	TSL:1	c.-13-2599_-13-2598insG		intron	N/A	ENSP00000422518.1

Frequencies

GnomAD3 genomes AF: 0.981 AC: 149106 AN: 151970 Hom.: 73217 Cov.: 0

Gnomad AFR AF: 0.934

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.990

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

GnomAD4 exome AF: 0.999 AC: 832020 AN: 833258 Hom.: 415430 Cov.: 4 AF XY: 0.999 AC XY: 384295 AN XY: 384830

African (AFR) AF: 0.933 AC: 14731 AN: 15786

American (AMR) AF: 1.00 AC: 986 AN: 986

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 5154 AN: 5154

East Asian (EAS) AF: 1.00 AC: 3640 AN: 3640

South Asian (SAS) AF: 1.00 AC: 16458 AN: 16460

European-Finnish (FIN) AF: 1.00 AC: 280 AN: 280

Middle Eastern (MID) AF: 0.996 AC: 1615 AN: 1622

European-Non Finnish (NFE) AF: 1.00 AC: 761961 AN: 762028

Other (OTH) AF: 0.996 AC: 27195 AN: 27302

GnomAD4 genome AF: 0.981 AC: 149211 AN: 152078 Hom.: 73267 Cov.: 0 AF XY: 0.982 AC XY: 72994 AN XY: 74340

African (AFR) AF: 0.934 AC: 38729 AN: 41464

American (AMR) AF: 0.995 AC: 15221 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5112 AN: 5112

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10602 AN: 10602

Middle Eastern (MID) AF: 0.990 AC: 289 AN: 292

European-Non Finnish (NFE) AF: 1.00 AC: 67958 AN: 67974

Other (OTH) AF: 0.987 AC: 2086 AN: 2114

Alfa AF: 0.989 Hom.: 7989

Asia WGS AF: 0.998 AC: 3464 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.074
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: rs10482610; hg19: chr5-142783015; COSMIC: COSV51540798; COSMIC: COSV51540798;