rs7300444

Positions:

chr12-884764-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_213655.5(WNK1):c.4716C>T(p.Asn1572=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,613,866 control chromosomes in the GnomAD database, including 151,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12482 hom., cov: 32)

Exomes 𝑓: 0.43 ( 139456 hom. )

Consequence

WNK1
NM_213655.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0590

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-884764-C-T is Benign according to our data. Variant chr12-884764-C-T is described in ClinVar as [Benign]. Clinvar id is 137925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-884764-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.059 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK1	NM_213655.5 linkuse as main transcript	c.4716C>T	p.Asn1572=	synonymous_variant	19/28	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4 linkuse as main transcript	c.3960C>T	p.Asn1320=	synonymous_variant	19/28	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9 linkuse as main transcript	c.4716C>T	p.Asn1572=	synonymous_variant	19/28	5	NM_213655.5	ENSP00000341292	A2	Q9H4A3-5
WNK1	ENST00000315939.11 linkuse as main transcript	c.3960C>T	p.Asn1320=	synonymous_variant	19/28	1	NM_018979.4	ENSP00000313059	P2	Q9H4A3-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60638

AN:

151882

Hom.:

12474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.421

AC:

105887

AN:

251434

Hom.:

22835

AF XY:

0.420

AC XY:

57017

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.525

Gnomad SAS exome

AF:

0.348

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.434

AC:

635010

AN:

1461866

Hom.:

139456

Cov.:

AF XY:

0.432

AC XY:

313991

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.514

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.399

AC:

60672

AN:

152000

Hom.:

12482

Cov.:

AF XY:

0.400

AC XY:

29708

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.417

Gnomad4 ASJ

AF:

0.387

Gnomad4 EAS

AF:

0.530

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.436

Gnomad4 NFE

AF:

0.441

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.425

Hom.:

32229

Bravo

AF:

0.396

Asia WGS

AF:

0.410

AC:

1425

AN:

3478

EpiCase

AF:

0.421

EpiControl

AF:

0.419

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	GeneDx	Dec 11, 2013	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. -

Pseudohypoaldosteronism type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

Athena Diagnostics

Jun 12, 2017

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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