chr4-148152404-C-T

Position:

• chr4-148152404-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000901.5(NR3C2):​c.2510+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,543,868 control chromosomes in the GnomAD database, including 413,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41612 hom., cov: 33)
  • Exomes 𝑓: 0.73 (371974 hom.)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00400

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 4-148152404-C-T is Benign according to our data. Variant chr4-148152404-C-T is described in ClinVar as [Benign]. Clinvar id is 1270506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C2	NM_000901.5	c.2510+65G>A		intron_variant		ENST00000358102.8	NP_000892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C2	ENST00000358102.8	c.2510+65G>A		intron_variant		1	NM_000901.5	ENSP00000350815.3

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112411 AN: 151990 Hom.: 41570 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.721

GnomAD4 exome AF: 0.730 AC: 1016354 AN: 1391760 Hom.: 371974 Cov.: 20 AF XY: 0.728 AC XY: 506930 AN XY: 695898

Gnomad4 AFR exome AF: 0.779

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.783

Gnomad4 EAS exome AF: 0.769

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.732

GnomAD4 genome AF: 0.740 AC: 112508 AN: 152108 Hom.: 41612 Cov.: 33 AF XY: 0.736 AC XY: 54706 AN XY: 74348

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.723

Alfa AF: 0.730 Hom.: 53756

Bravo AF: 0.742

Asia WGS AF: 0.721 AC: 2511 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.51

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: rs2272089; hg19: chr4-149073555;