rs11099694

chr4-148346557-G-A

Variant summary

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

The NM_000901.5(NR3C2):c.1758-86440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 151,802 control chromosomes in the GnomAD database, including 38,184 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 0.70 (38184 hom., cov: 30)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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 (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR3C2	NM_000901.5	c.1758-86440C>T		intron_variant		ENST00000358102.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR3C2	ENST00000358102.8	c.1758-86440C>T		intron_variant		1	NM_000901.5	P4

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106117 AN: 151682 Hom.: 38137 Cov.: 30

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.700 AC: 106226 AN: 151802 Hom.: 38184 Cov.: 30 AF XY: 0.694 AC XY: 51465 AN XY: 74142

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.689

Alfa AF: 0.666 Hom.: 14706

Bravo AF: 0.701

Asia WGS AF: 0.542 AC: 1888 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	3.2
Dann	Benign	0.28

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: rs11099694; hg19: chr4-149267709;