rs17484245

Positions:

• chr4-148259823-G-A
• chr4-148259823-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000901.5(NR3C2):​c.1897+155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 901,370 control chromosomes in the GnomAD database, including 15,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2721 hom., cov: 33)
  • Exomes 𝑓: 0.18 (13270 hom.)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.316

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-148259823-G-A is Benign according to our data. Variant chr4-148259823-G-A is described in ClinVar as [Benign]. Clinvar id is 1259025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR3C2	NM_000901.5	c.1897+155C>T		intron_variant		ENST00000358102.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR3C2	ENST00000358102.8	c.1897+155C>T		intron_variant		1	NM_000901.5	P4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28095 AN: 152018 Hom.: 2719 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.185 AC: 138457 AN: 749234 Hom.: 13270 AF XY: 0.186 AC XY: 72411 AN XY: 388430

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.185 AC: 28114 AN: 152136 Hom.: 2721 Cov.: 33 AF XY: 0.189 AC XY: 14037 AN XY: 74366

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.190

Alfa AF: 0.174 Hom.: 309

Bravo AF: 0.188

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.40

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: rs17484245; hg19: chr4-149180975;