rs879206

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000358102.8(NR3C2):​c.1757+20848C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,044 control chromosomes in the GnomAD database, including 6,592 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 0.25 ( 6592 hom., cov: 32)

Consequence

NR3C2
ENST00000358102.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NR3C2NM_000901.5 linkuse as main transcriptc.1757+20848C>A intron_variant ENST00000358102.8 NP_000892.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NR3C2ENST00000358102.8 linkuse as main transcriptc.1757+20848C>A intron_variant 1 NM_000901.5 ENSP00000350815 P4P08235-1

Frequencies

GnomAD3 genomes
AF:
0.254
AC:
38633
AN:
151926
Hom.:
6566
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.486
Gnomad AMI
AF:
0.197
Gnomad AMR
AF:
0.203
Gnomad ASJ
AF:
0.159
Gnomad EAS
AF:
0.159
Gnomad SAS
AF:
0.180
Gnomad FIN
AF:
0.110
Gnomad MID
AF:
0.212
Gnomad NFE
AF:
0.166
Gnomad OTH
AF:
0.250
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.255
AC:
38725
AN:
152044
Hom.:
6592
Cov.:
32
AF XY:
0.250
AC XY:
18556
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.486
Gnomad4 AMR
AF:
0.203
Gnomad4 ASJ
AF:
0.159
Gnomad4 EAS
AF:
0.160
Gnomad4 SAS
AF:
0.181
Gnomad4 FIN
AF:
0.110
Gnomad4 NFE
AF:
0.166
Gnomad4 OTH
AF:
0.253
Alfa
AF:
0.250
Hom.:
891
Bravo
AF:
0.271
Asia WGS
AF:
0.198
AC:
688
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.1
DANN
Benign
0.80

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs879206; hg19: chr4-149335408; API