Genetic Variant WNK1:c.760-14525C>T (chr12-799117-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_213655.5(WNK1):c.760-14525C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,880 control chromosomes in the GnomAD database, including 34,945 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 0.68 ( 34945 hom., cov: 30)

Consequence

WNK1
NM_213655.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.576

Publications

14 publications found

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 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

WNK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5 link	c.760-14525C>T		intron_variant	Intron 1 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4 link	c.760-14525C>T		intron_variant	Intron 1 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9 link	c.760-14525C>T		intron_variant	Intron 1 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11 link	c.760-14525C>T		intron_variant	Intron 1 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

102500

AN:

151762

Hom.:

34928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.875

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.690

Gnomad OTH

AF:

0.648

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

GnomAD4 genome

AF:

0.675

AC:

102566

AN:

151880

Hom.:

34945

Cov.:

AF XY:

0.679

AC XY:

50427

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.601

AC:

24876

AN:

41364

American (AMR)

AF:

0.704

AC:

10745

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2048

AN:

3470

East Asian (EAS)

AF:

0.874

AC:

4531

AN:

5182

South Asian (SAS)

AF:

0.716

AC:

3453

AN:

4822

European-Finnish (FIN)

AF:

0.743

AC:

7820

AN:

10524

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.690

AC:

46876

AN:

67958

Other (OTH)

AF:

0.644

AC:

1357

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1667

3334

5001

6668

8335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.693

Hom.:

10707

Bravo

AF:

0.669

Asia WGS

AF:

0.746

AC:

2592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.35

PhyloP100

-0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over