4-148391417-C-A

Position:

• chr4-148391417-C-A

Variant summary

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

The NM_000901.5(NR3C2):​c.1757+43687G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,180 control chromosomes in the GnomAD database, including 980 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 0.10 (980 hom., cov: 32)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C2	NM_000901.5	c.1757+43687G>T		intron_variant		ENST00000358102.8	NP_000892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C2	ENST00000358102.8	c.1757+43687G>T		intron_variant		1	NM_000901.5	ENSP00000350815	P4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15777 AN: 152062 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0631

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.104 AC: 15764 AN: 152180 Hom.: 980 Cov.: 32 AF XY: 0.0996 AC XY: 7412 AN XY: 74404

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0631

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.124

Alfa AF: 0.117 Hom.: 209

Bravo AF: 0.106

Asia WGS AF: 0.0360 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
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: rs10519958; hg19: chr4-149312569;