rs10774461

chr12-784801-C-Achr12-784801-C-Gchr12-784801-C-T

Variant summary

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

The NM_213655.5(WNK1):c.760-28841C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,928 control chromosomes in the GnomAD database, including 18,244 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 0.48 (18244 hom., cov: 32)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.760-28841C>A		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.760-28841C>A		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.760-28841C>A		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.760-28841C>A		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73557 AN: 151810 Hom.: 18238 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.484 AC: 73603 AN: 151928 Hom.: 18244 Cov.: 32 AF XY: 0.483 AC XY: 35870 AN XY: 74250

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.473

Alfa AF: 0.495 Hom.: 19840

Bravo AF: 0.488

Asia WGS AF: 0.560 AC: 1942 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.5
Dann	Benign	0.70

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: rs10774461; hg19: chr12-893967;