rs11064573

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_213655.5(WNK1):c.1401-11C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,600,484 control chromosomes in the GnomAD database, including 19,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1487 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17824 hom. )

Consequence

WNK1
NM_213655.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0004055

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.346

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-859234-C-A is Benign according to our data. Variant chr12-859234-C-A is described in ClinVar as [Benign]. Clinvar id is 137922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-859234-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4 linkuse as main transcript	c.1401-11C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000315939.11
WNK1	NM_213655.5 linkuse as main transcript	c.1401-11C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11 linkuse as main transcript	c.1401-11C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018979.4	P2	Q9H4A3-1
WNK1	ENST00000340908.9 linkuse as main transcript	c.1401-11C>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_213655.5	A2	Q9H4A3-5

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19084

AN:

151852

Hom.:

1486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.0898

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0611

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.146

AC:

36423

AN:

249398

Hom.:

3300

AF XY:

0.153

AC XY:

20721

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.0476

Gnomad AMR exome

AF:

0.0689

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0666

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.151

AC:

218187

AN:

1448514

Hom.:

17824

Cov.:

AF XY:

0.153

AC XY:

110161

AN XY:

721532

show subpopulations

Gnomad4 AFR exome

AF:

0.0453

Gnomad4 AMR exome

AF:

0.0710

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0487

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.126

AC:

19095

AN:

151970

Hom.:

1487

Cov.:

AF XY:

0.130

AC XY:

9647

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0508

Gnomad4 AMR

AF:

0.0897

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0612

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.101

Hom.:

230

Bravo

AF:

0.107

Asia WGS

AF:

0.106

AC:

369

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Pseudohypoaldosteronism type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Neuropathy, hereditary sensory and autonomic, type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

Dann

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00041

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over