rs11064519

Variant names:

• chr12-762045-G-C
• rs11064519
• NM_213655.5:c.759+7721G>C

Variant summary

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

The NM_018979.4(WNK1):​c.759+7721G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 141,838 control chromosomes in the GnomAD database, including 28,350 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 0.59 (28350 hom., cov: 25)
• Consequence: WNK1 NM_018979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 2 publications found

Genes affected

WNK1 (HGNC:14540): (WNK lysine deficient protein kinase 1) This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]

WNK1 Gene-Disease associations (from GenCC):

• neuropathy, hereditary sensory and autonomic, type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
• pseudohypoaldosteronism type 2C

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	NM_213655.5	MANE Plus Clinical	c.759+7721G>C		intron	N/A	NP_998820.3
	WNK1	NM_018979.4	MANE Select	c.759+7721G>C		intron	N/A	NP_061852.3
	WNK1	NM_001184985.2		c.759+7721G>C		intron	N/A	NP_001171914.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	ENST00000340908.9	TSL:5 MANE Plus Clinical	c.759+7721G>C		intron	N/A	ENSP00000341292.5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.759+7721G>C		intron	N/A	ENSP00000313059.6
	WNK1	ENST00000530271.6	TSL:1	c.759+7721G>C		intron	N/A	ENSP00000433548.3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 84179 AN: 141714 Hom.: 28354 Cov.: 25

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.549

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.594 AC: 84213 AN: 141838 Hom.: 28350 Cov.: 25 AF XY: 0.595 AC XY: 40680 AN XY: 68336

African (AFR) AF: 0.438 AC: 17500 AN: 39978

American (AMR) AF: 0.585 AC: 8320 AN: 14222

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1771 AN: 3312

East Asian (EAS) AF: 0.867 AC: 4368 AN: 5040

South Asian (SAS) AF: 0.681 AC: 2981 AN: 4378

European-Finnish (FIN) AF: 0.638 AC: 4934 AN: 7732

Middle Eastern (MID) AF: 0.545 AC: 146 AN: 268

European-Non Finnish (NFE) AF: 0.662 AC: 42487 AN: 64170

Other (OTH) AF: 0.584 AC: 1122 AN: 1922

Alfa AF: 0.611 Hom.: 3453

Asia WGS AF: 0.714 AC: 2436 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.25
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: rs11064519; hg19: chr12-871211;