rs6856803

Variant names:

• chr4-148165976-T-C
• rs6856803
• NM_000901.5:c.2015-11075A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-148165976-T-C
• chr4-148165976-T-G

Variant summary

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

The NM_000901.5(NR3C2):​c.2015-11075A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,034 control chromosomes in the GnomAD database, including 15,264 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 0.44 (15264 hom., cov: 32)
• Consequence: NR3C2 NM_000901.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR3C2	NM_000901.5	c.2015-11075A>G		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.2015-11075A>G		intron_variant	Intron 4 of 8	1	NM_000901.5	ENSP00000350815.3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67289 AN: 151914 Hom.: 15244 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.443 AC: 67359 AN: 152034 Hom.: 15264 Cov.: 32 AF XY: 0.437 AC XY: 32444 AN XY: 74316

African (AFR) AF: 0.532 AC: 22081 AN: 41486

American (AMR) AF: 0.462 AC: 7063 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1212 AN: 3462

East Asian (EAS) AF: 0.522 AC: 2702 AN: 5178

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3517 AN: 10552

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27825 AN: 67940

Other (OTH) AF: 0.432 AC: 912 AN: 2112

Alfa AF: 0.420 Hom.: 36335

Bravo AF: 0.459

Asia WGS AF: 0.420 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-0.73
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: rs6856803; hg19: chr4-149087127;