rs1490453

Positions:

• chr4-148400194-G-A

Variant summary

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

The NM_000901.5(NR3C2):​c.1757+34910C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,110 control chromosomes in the GnomAD database, including 4,499 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 0.22 (4499 hom., cov: 33)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

Genes affected

NR3C2 (HGNC:7979): (nuclear receptor subfamily 3 group C member 2) This gene encodes the mineralocorticoid receptor, which mediates aldosterone actions on salt and water balance within restricted target cells. The protein functions as a ligand-dependent transcription factor that binds to mineralocorticoid response elements in order to transactivate target genes. Mutations in this gene cause autosomal dominant pseudohypoaldosteronism type I, a disorder characterized by urinary salt wasting. Defects in this gene are also associated with early onset hypertension with severe exacerbation in pregnancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C2	NM_000901.5	c.1757+34910C>T		intron_variant		ENST00000358102.8	NP_000892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C2	ENST00000358102.8	c.1757+34910C>T		intron_variant		1	NM_000901.5	ENSP00000350815	P4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32733 AN: 151992 Hom.: 4491 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.215 AC: 32773 AN: 152110 Hom.: 4499 Cov.: 33 AF XY: 0.208 AC XY: 15502 AN XY: 74374

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.214

Alfa AF: 0.169 Hom.: 5241

Bravo AF: 0.226

Asia WGS AF: 0.0780 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs1490453; hg19: chr4-149321346;