rs10849582

Variant names:

• chr12-904010-A-G
• rs10849582
• NM_213655.5:c.7399+3340A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018979.4(WNK1):​c.6643+3340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,102 control chromosomes in the GnomAD database, including 16,476 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 0.46 (16476 hom., cov: 32)
• Consequence: WNK1 NM_018979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	NM_213655.5	MANE Plus Clinical	c.7399+3340A>G		intron	N/A	NP_998820.3	Q9H4A3-5
	WNK1	NM_018979.4	MANE Select	c.6643+3340A>G		intron	N/A	NP_061852.3	Q9H4A3-1
	WNK1	NM_001184985.2		c.7423+3340A>G		intron	N/A	NP_001171914.1	Q9H4A3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	ENST00000340908.9	TSL:5 MANE Plus Clinical	c.7399+3340A>G		intron	N/A	ENSP00000341292.5	Q9H4A3-5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.6643+3340A>G		intron	N/A	ENSP00000313059.6	Q9H4A3-1
	WNK1	ENST00000530271.6	TSL:1	c.7955-443A>G		intron	N/A	ENSP00000433548.3	Q9H4A3-7

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69146 AN: 151984 Hom.: 16451 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.455 AC: 69221 AN: 152102 Hom.: 16476 Cov.: 32 AF XY: 0.450 AC XY: 33471 AN XY: 74350

African (AFR) AF: 0.583 AC: 24184 AN: 41476

American (AMR) AF: 0.455 AC: 6944 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1593 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1514 AN: 5174

South Asian (SAS) AF: 0.507 AC: 2442 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3158 AN: 10578

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27958 AN: 67988

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.429 Hom.: 13898

Bravo AF: 0.469

Asia WGS AF: 0.442 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.028
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: rs10849582; hg19: chr12-1013176;