12-780667-A-G

Position:

• chr12-780667-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018979.4(WNK1):​c.759+26343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,100 control chromosomes in the GnomAD database, including 24,964 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 0.57 (24964 hom., cov: 33)
• Consequence: WNK1 NM_018979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK1	NM_213655.5	c.759+26343A>G		intron_variant		ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.759+26343A>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.759+26343A>G		intron_variant		5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.759+26343A>G		intron_variant		1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86388 AN: 151980 Hom.: 24951 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.568 AC: 86442 AN: 152100 Hom.: 24964 Cov.: 33 AF XY: 0.568 AC XY: 42213 AN XY: 74356

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.570

Alfa AF: 0.592 Hom.: 44452

Bravo AF: 0.571

Asia WGS AF: 0.637 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.89

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: rs11608756; hg19: chr12-889833;