rs3910044

Positions:

• chr4-148226671-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000901.5(NR3C2):​c.1898-31809A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,948 control chromosomes in the GnomAD database, including 24,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24292 hom., cov: 31)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR3C2	NM_000901.5	c.1898-31809A>G		intron_variant		ENST00000358102.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR3C2	ENST00000358102.8	c.1898-31809A>G		intron_variant		1	NM_000901.5	P4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85384 AN: 151832 Hom.: 24263 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.562 AC: 85460 AN: 151948 Hom.: 24292 Cov.: 31 AF XY: 0.558 AC XY: 41405 AN XY: 74254

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.588

Alfa AF: 0.599 Hom.: 39085

Bravo AF: 0.565

Asia WGS AF: 0.462 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.91
DANN	Benign	0.59

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: rs3910044; hg19: chr4-149147823;