rs7694064

Variant names:

• chr4-148162067-A-G
• rs7694064
• NM_000901.5:c.2015-7166T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-148162067-A-G
• chr4-148162067-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000901.5(NR3C2):​c.2015-7166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,072 control chromosomes in the GnomAD database, including 41,976 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 0.74 (41976 hom., cov: 31)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant pseudohypoaldosteronism type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pseudohyperaldosteronism type 2

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000250354 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C2	NM_000901.5	c.2015-7166T>C		intron_variant	Intron 4 of 8	ENST00000358102.8	NP_000892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR3C2	ENST00000358102.8	c.2015-7166T>C		intron_variant	Intron 4 of 8	1	NM_000901.5	ENSP00000350815.3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112820 AN: 151952 Hom.: 41937 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.742 AC: 112912 AN: 152072 Hom.: 41976 Cov.: 31 AF XY: 0.738 AC XY: 54872 AN XY: 74350

African (AFR) AF: 0.790 AC: 32780 AN: 41474

American (AMR) AF: 0.703 AC: 10738 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2708 AN: 3464

East Asian (EAS) AF: 0.708 AC: 3660 AN: 5166

South Asian (SAS) AF: 0.667 AC: 3205 AN: 4806

European-Finnish (FIN) AF: 0.710 AC: 7507 AN: 10572

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49871 AN: 68004

Other (OTH) AF: 0.726 AC: 1528 AN: 2104

Alfa AF: 0.736 Hom.: 22482

Bravo AF: 0.745

Asia WGS AF: 0.707 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.59
DANN	Benign	0.61
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7694064; hg19: chr4-149083218;