rs7719514

Positions:

• chr5-143430559-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504572.5(NR3C1):​c.-14+3160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 152,214 control chromosomes in the GnomAD database, including 297 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 0.060 (297 hom., cov: 32)
• Consequence: NR3C1 ENST00000504572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_001018074.1	c.-14+4645C>T		intron_variant			NP_001018084.1
NR3C1	NM_001018075.1	c.-14+4742C>T		intron_variant			NP_001018085.1
NR3C1	NM_001018077.1	c.-14+3973C>T		intron_variant			NP_001018087.1
NR3C1	NM_001364183.2	c.-14+3160C>T		intron_variant			NP_001351112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-14+3160C>T		intron_variant		1		ENSP00000422518	P4
NR3C1	ENST00000343796.6	c.-14+3973C>T		intron_variant		5		ENSP00000343205	A1
NR3C1	ENST00000503701.1	n.352+3160C>T		intron_variant, non_coding_transcript_variant		3
NR3C1	ENST00000505058.5	n.241+3973C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9189 AN: 152096 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0604 AC: 9190 AN: 152214 Hom.: 297 Cov.: 32 AF XY: 0.0627 AC XY: 4665 AN XY: 74418

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0550

Gnomad4 OTH AF: 0.0748

Alfa AF: 0.0537 Hom.: 43

Bravo AF: 0.0580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7719514; hg19: chr5-142810124;