rs10482714

Variant names:

• chr5-143278339-C-T
• rs10482714
• NM_000176.3:c.*3550G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-143278339-C-T
• chr5-143278339-C-A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_000176.3(NR3C1):​c.*3550G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 152,234 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (20 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NR3C1 NM_000176.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.84
• 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: Orphanet, Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000300303 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 5-143278339-C-T is Benign according to our data. Variant chr5-143278339-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 351316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0101 (1534/152234) while in subpopulation SAS AF = 0.0211 (102/4828). AF 95% confidence interval is 0.0178. There are 20 homozygotes in GnomAd4. There are 855 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1534 AD gene.

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.*3550G>A		3_prime_UTR	Exon 9 of 9	NP_000167.1	P04150-1
	NR3C1	NM_001024094.2		c.*3550G>A		3_prime_UTR	Exon 9 of 9	NP_001019265.1	E5KQF6
	NR3C1	NM_001364183.2		c.*3550G>A		3_prime_UTR	Exon 10 of 10	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.*3550G>A		3_prime_UTR	Exon 9 of 9	ENSP00000377977.2	P04150-1
	NR3C1	ENST00000415690.6	TSL:1	c.*1025G>A		3_prime_UTR	Exon 9 of 9	ENSP00000387672.2	P04150-2
	NR3C1	ENST00000343796.6	TSL:5	c.*3550G>A		3_prime_UTR	Exon 9 of 9	ENSP00000343205.2	P04150-1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1535 AN: 152118 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00910

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0101 AC: 1534 AN: 152234 Hom.: 20 Cov.: 32 AF XY: 0.0115 AC XY: 855 AN XY: 74424

African (AFR) AF: 0.00166 AC: 69 AN: 41548

American (AMR) AF: 0.00399 AC: 61 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4828

European-Finnish (FIN) AF: 0.0509 AC: 539 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0103 AC: 704 AN: 68024

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00924 Hom.: 26

Bravo AF: 0.00574

Asia WGS AF: 0.00867 AC: 30 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Glucocorticoid resistance (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

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: rs10482714; hg19: chr5-142657904;