12-879392-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213655.5(WNK1):c.3867+1031C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 149,340 control chromosomes in the GnomAD database, including 22,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (22974 hom., cov: 28)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0720

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-879392-C-T is Benign according to our data. Variant chr12-879392-C-T is described in ClinVar as [Benign]. Clinvar id is 538531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.2374-181C>T		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.3867+1031C>T		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.2374-181C>T		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.3867+1031C>T		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 81743 AN: 149252 Hom.: 22969 Cov.: 28

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.548 AC: 81779 AN: 149340 Hom.: 22974 Cov.: 28 AF XY: 0.552 AC XY: 40141 AN XY: 72710

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.530

Alfa AF: 0.566 Hom.: 6941

Bravo AF: 0.533

Asia WGS AF: 0.558 AC: 1939 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	6.9
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs880054; hg19: chr12-988558;