rs17484245

Variant names:

• chr4-148259823-G-A
• rs17484245
• NM_000901.5:c.1897+155C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

NR3C2 Gene-Disease associations (from GenCC):

• autosomal dominant pseudohypoaldosteronism type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Illumina, Ambry Genetics
• pseudohyperaldosteronism type 2

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000901.5. 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
	NR3C2	NM_000901.5	MANE Select	c.1897+155C>T		intron	N/A	NP_000892.2	B0ZBF6
	NR3C2	NM_001437657.1		c.1909+143C>T		intron	N/A	NP_001424586.1
	NR3C2	NM_001437654.1		c.1897+155C>T		intron	N/A	NP_001424583.1	B0ZBF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR3C2	ENST00000358102.8	TSL:1 MANE Select	c.1897+155C>T		intron	N/A	ENSP00000350815.3	P08235-1
	NR3C2	ENST00000512865.5	TSL:1	c.1897+155C>T		intron	N/A	ENSP00000423510.1	P08235-4
	NR3C2	ENST00000511528.1	TSL:5	c.1909+143C>T		intron	N/A	ENSP00000421481.1	P08235-3

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

African (AFR) AF: 0.148 AC: 2661 AN: 18014

American (AMR) AF: 0.263 AC: 7067 AN: 26848

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 3675 AN: 18236

East Asian (EAS) AF: 0.203 AC: 6859 AN: 33858

South Asian (SAS) AF: 0.215 AC: 12408 AN: 57738

European-Finnish (FIN) AF: 0.178 AC: 6627 AN: 37158

Middle Eastern (MID) AF: 0.190 AC: 505 AN: 2658

European-Non Finnish (NFE) AF: 0.177 AC: 91862 AN: 518666

Other (OTH) AF: 0.188 AC: 6793 AN: 36058

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

African (AFR) AF: 0.148 AC: 6144 AN: 41498

American (AMR) AF: 0.265 AC: 4053 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1067 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4824

European-Finnish (FIN) AF: 0.192 AC: 2036 AN: 10578

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12169 AN: 67996

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.174 Hom.: 309

Bravo AF: 0.188

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.40
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs17484245; hg19: chr4-149180975;