rs1159744

Positions:

• chr12-825679-C-G
• chr12-825679-C-T

Variant summary

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

The NM_018979.4(WNK1):​c.933-1363C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,032 control chromosomes in the GnomAD database, including 43,957 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 0.76 (43957 hom., cov: 31)
• Consequence: WNK1 NM_018979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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/exons	MANE	Protein	UniProt
WNK1	NM_213655.5	c.933-1363C>G		intron_variant		ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.933-1363C>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.933-1363C>G		intron_variant		5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.933-1363C>G		intron_variant		1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115407 AN: 151912 Hom.: 43911 Cov.: 31

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.760 AC: 115508 AN: 152032 Hom.: 43957 Cov.: 31 AF XY: 0.763 AC XY: 56659 AN XY: 74306

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.735

Alfa AF: 0.759 Hom.: 5453

Bravo AF: 0.756

Asia WGS AF: 0.776 AC: 2681 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.78

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: rs1159744; hg19: chr12-934845;