rs6816503

Positions:

• chr4-148163296-G-T

Variant summary

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

The NM_000901.5(NR3C2):​c.2015-8395C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,162 control chromosomes in the GnomAD database, including 3,213 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 0.17 (3213 hom., cov: 32)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C2	NM_000901.5	c.2015-8395C>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.2015-8395C>A		intron_variant		1	NM_000901.5	ENSP00000350815	P4
	ENST00000514843.1	n.79+16747G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25377 AN: 152044 Hom.: 3198 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.167 AC: 25427 AN: 152162 Hom.: 3213 Cov.: 32 AF XY: 0.168 AC XY: 12520 AN XY: 74394

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0821

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.130

Alfa AF: 0.130 Hom.: 322

Bravo AF: 0.169

Asia WGS AF: 0.138 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.83

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: rs6816503; hg19: chr4-149084447;