rs12816718

Positions:

• chr12-860634-G-T

Variant summary

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

The NM_213655.5(WNK1):​c.1621-379G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,166 control chromosomes in the GnomAD database, including 2,234 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 0.17 (2234 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK1	NM_018979.4	c.1621-379G>T		intron_variant		ENST00000315939.11	NP_061852.3
WNK1	NM_213655.5	c.1621-379G>T		intron_variant		ENST00000340908.9	NP_998820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000315939.11	c.1621-379G>T		intron_variant		1	NM_018979.4	ENSP00000313059	P2
WNK1	ENST00000340908.9	c.1621-379G>T		intron_variant		5	NM_213655.5	ENSP00000341292	A2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25131 AN: 152048 Hom.: 2230 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.165 AC: 25161 AN: 152166 Hom.: 2234 Cov.: 31 AF XY: 0.168 AC XY: 12493 AN XY: 74368

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.149

Alfa AF: 0.162 Hom.: 1113

Bravo AF: 0.153

Asia WGS AF: 0.121 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.52

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: rs12816718; hg19: chr12-969800;