Variant chr12-894671-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_213655.5(WNK1):c.6339+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,586,762 control chromosomes in the GnomAD database, including 47,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4743 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42519 hom. )

Consequence

WNK1
NM_213655.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.836

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=-0.94).

BP6

Variant 12-894671-C-T is Benign according to our data. Variant chr12-894671-C-T is described in ClinVar as [Benign]. Clinvar id is 674135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-894671-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 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.5583+36C>T		intron_variant		ENST00000315939.11
WNK1	NM_213655.5 linkuse as main transcript	c.6339+36C>T		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11 linkuse as main transcript	c.5583+36C>T		intron_variant		1	NM_018979.4	P2	Q9H4A3-1
WNK1	ENST00000340908.9 linkuse as main transcript	c.6339+36C>T		intron_variant		5	NM_213655.5	A2	Q9H4A3-5

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37669

AN:

151916

Hom.:

4738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.236

AC:

59206

AN:

251250

Hom.:

7279

AF XY:

0.236

AC XY:

32103

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.277

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.242

AC:

347147

AN:

1434730

Hom.:

42519

Cov.:

AF XY:

0.242

AC XY:

173385

AN XY:

715544

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.195

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.248

AC:

37703

AN:

152032

Hom.:

4743

Cov.:

AF XY:

0.245

AC XY:

18223

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.252

Hom.:

1118

Bravo

AF:

0.252

Asia WGS

AF:

0.255

AC:

885

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	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. -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

8.1

DANN

Benign

0.63

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