chr12-789234-C-A

Position:

• chr12-789234-C-A

Variant summary

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

The ENST00000315939.11(WNK1):​c.760-24408C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,942 control chromosomes in the GnomAD database, including 38,750 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 0.71 (38750 hom., cov: 30)
• Consequence: WNK1 ENST00000315939.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK1	NM_018979.4	c.760-24408C>A		intron_variant		ENST00000315939.11	NP_061852.3
WNK1	NM_213655.5	c.760-24408C>A		intron_variant		ENST00000340908.9	NP_998820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000315939.11	c.760-24408C>A		intron_variant		1	NM_018979.4	ENSP00000313059	P2
WNK1	ENST00000340908.9	c.760-24408C>A		intron_variant		5	NM_213655.5	ENSP00000341292	A2

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107519 AN: 151822 Hom.: 38728 Cov.: 30

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.708 AC: 107592 AN: 151942 Hom.: 38750 Cov.: 30 AF XY: 0.711 AC XY: 52788 AN XY: 74286

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.698

Alfa AF: 0.740 Hom.: 17937

Bravo AF: 0.700

Asia WGS AF: 0.730 AC: 2537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.45

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: rs724709; hg19: chr12-898400;