rs36052085

Positions:

• chr12-852703-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018979.4(WNK1):​c.1312-4458C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,124 control chromosomes in the GnomAD database, including 1,468 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 0.12 (1468 hom., cov: 32)
• Consequence: WNK1 NM_018979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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	Protein	UniProt
WNK1	NM_213655.5	c.1312-4458C>G		intron_variant		ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.1312-4458C>G		intron_variant		ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.1312-4458C>G		intron_variant		5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.1312-4458C>G		intron_variant		1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18460 AN: 152006 Hom.: 1467 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.121 AC: 18468 AN: 152124 Hom.: 1468 Cov.: 32 AF XY: 0.126 AC XY: 9374 AN XY: 74368

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0615

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.118

Alfa AF: 0.136 Hom.: 191

Bravo AF: 0.103

Asia WGS AF: 0.105 AC: 367 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.38

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: rs36052085; hg19: chr12-961869;