rs10774461

Variant names:

• chr12-784801-C-A
• rs10774461
• NM_213655.5:c.760-28841C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-784801-C-A
• chr12-784801-C-G
• chr12-784801-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

WNK1 Gene-Disease associations (from GenCC):

• neuropathy, hereditary sensory and autonomic, type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
• pseudohypoaldosteronism type 2C

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.760-28841C>A		intron_variant	Intron 1 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.760-28841C>A		intron_variant	Intron 1 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.760-28841C>A		intron_variant	Intron 1 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.760-28841C>A		intron_variant	Intron 1 of 27	1	NM_018979.4	ENSP00000313059.6

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

African (AFR) AF: 0.398 AC: 16507 AN: 41424

American (AMR) AF: 0.504 AC: 7700 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3470

East Asian (EAS) AF: 0.776 AC: 4008 AN: 5166

South Asian (SAS) AF: 0.454 AC: 2185 AN: 4812

European-Finnish (FIN) AF: 0.448 AC: 4726 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35493 AN: 67934

Other (OTH) AF: 0.473 AC: 997 AN: 2106

Alfa AF: 0.498 Hom.: 29671

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
PhyloP100		0.023
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10774461; hg19: chr12-893967;