dbSNP rs17484245: NR3C2:c.1897+155C>T (chr4-148259823-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.316

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]

NR3C2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
NR3C2	NM_000901.5 link	c.1897+155C>T		intron_variant	Intron 3 of 8	ENST00000358102.8	NP_000892.2	P08235-1B0ZBF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C2	ENST00000358102.8 link	c.1897+155C>T		intron_variant	Intron 3 of 8	1	NM_000901.5	ENSP00000350815.3		P08235-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28095

AN:

152018

Hom.:

2719

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.189

AC XY:

14037

AN XY:

74366

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over