Variant 4-148081516-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000358102.8(NR3C2):c.2800-17C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,613,876 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 25 hom., cov: 32)

Exomes 𝑓: 0.016 ( 225 hom. )

Consequence

NR3C2
ENST00000358102.8 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.375

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=-0.83).

BP6

Variant 4-148081516-G-C is Benign according to our data. Variant chr4-148081516-G-C is described in ClinVar as [Benign]. Clinvar id is 256831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-148081516-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1827/152306) while in subpopulation NFE AF= 0.0193 (1311/68028). AF 95% confidence interval is 0.0184. There are 25 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1827 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C2	NM_000901.5 linkuse as main transcript	c.2800-17C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000358102.8	NP_000892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C2	ENST00000358102.8 linkuse as main transcript	c.2800-17C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000901.5	ENSP00000350815	P4	P08235-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1826

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0123

AC:

3073

AN:

250434

Hom.:

AF XY:

0.0122

AC XY:

1656

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.00266

Gnomad AMR exome

AF:

0.00469

Gnomad ASJ exome

AF:

0.00269

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0161

AC:

23557

AN:

1461570

Hom.:

225

Cov.:

AF XY:

0.0157

AC XY:

11441

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.0201

Gnomad4 NFE exome

AF:

0.0190

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0120

AC:

1827

AN:

152306

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

877

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00320

Gnomad4 AMR

AF:

0.00725

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0202

Gnomad4 NFE

AF:

0.0193

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00628

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.55

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