dbSNP rs1879829: NR3C2:c.2642-37A>G (chr4-148114298-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000901.5(NR3C2):c.2642-37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,609,708 control chromosomes in the GnomAD database, including 174,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16650 hom., cov: 33)

Exomes 𝑓: 0.46 ( 158118 hom. )

Consequence

NR3C2
NM_000901.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0110

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 4-148114298-T-C is Benign according to our data. Variant chr4-148114298-T-C is described in ClinVar as [Benign]. Clinvar id is 1236999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C2	NM_000901.5 link	c.2642-37A>G		intron_variant	Intron 7 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.2642-37A>G		intron_variant	Intron 7 of 8	1	NM_000901.5	ENSP00000350815.3		P08235-1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70524

AN:

151956

Hom.:

16640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.448

GnomAD3 exomes

AF:

0.486

AC:

119923

AN:

246940

Hom.:

29591

AF XY:

0.482

AC XY:

64245

AN XY:

133344

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.398

Gnomad EAS exome

AF:

0.677

Gnomad SAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.463

AC:

675222

AN:

1457634

Hom.:

158118

Cov.:

AF XY:

0.462

AC XY:

334976

AN XY:

724628

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.664

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.551

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.455

GnomAD4 genome

AF:

0.464

AC:

70567

AN:

152074

Hom.:

16650

Cov.:

AF XY:

0.465

AC XY:

34583

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.456

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.664

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.449

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.448

Hom.:

31255

Bravo

AF:

0.458

Asia WGS

AF:

0.540

AC:

1873

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.86

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