rs11064573

Variant names:

• chr12-859234-C-A
• rs11064573
• NM_213655.5:c.1401-11C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-859234-C-A
• chr12-859234-C-G
• chr12-859234-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018979.4(WNK1):​c.1401-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,600,484 control chromosomes in the GnomAD database, including 19,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1487 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17824 hom.)
• Consequence: WNK1 NM_018979.4 intron
• Scores: Splicing: ADA: 0.0004055
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.346
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-859234-C-A is Benign according to our data. Variant chr12-859234-C-A is described in ClinVar as Benign. ClinVar VariationId is 137922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 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.1401-11C>A		intron	N/A	NP_998820.3
	WNK1	NM_018979.4	MANE Select	c.1401-11C>A		intron	N/A	NP_061852.3
	WNK1	NM_001184985.2		c.1401-11C>A		intron	N/A	NP_001171914.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	ENST00000340908.9	TSL:5 MANE Plus Clinical	c.1401-11C>A		intron	N/A	ENSP00000341292.5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.1401-11C>A		intron	N/A	ENSP00000313059.6
	WNK1	ENST00000530271.6	TSL:1	c.1401-11C>A		intron	N/A	ENSP00000433548.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19084 AN: 151852 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.146 AC: 36423 AN: 249398 AF XY: 0.153

Gnomad AFR exome AF: 0.0476

Gnomad AMR exome AF: 0.0689

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0666

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.151 AC: 218187 AN: 1448514 Hom.: 17824 Cov.: 30 AF XY: 0.153 AC XY: 110161 AN XY: 721532

African (AFR) AF: 0.0453 AC: 1505 AN: 33236

American (AMR) AF: 0.0710 AC: 3169 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3964 AN: 26008

East Asian (EAS) AF: 0.0487 AC: 1926 AN: 39526

South Asian (SAS) AF: 0.185 AC: 15829 AN: 85746

European-Finnish (FIN) AF: 0.266 AC: 14176 AN: 53374

Middle Eastern (MID) AF: 0.205 AC: 1177 AN: 5742

European-Non Finnish (NFE) AF: 0.152 AC: 167560 AN: 1100300

Other (OTH) AF: 0.148 AC: 8881 AN: 59942

GnomAD4 genome AF: 0.126 AC: 19095 AN: 151970 Hom.: 1487 Cov.: 32 AF XY: 0.130 AC XY: 9647 AN XY: 74246

African (AFR) AF: 0.0508 AC: 2109 AN: 41478

American (AMR) AF: 0.0897 AC: 1370 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3464

East Asian (EAS) AF: 0.0612 AC: 317 AN: 5178

South Asian (SAS) AF: 0.170 AC: 820 AN: 4822

European-Finnish (FIN) AF: 0.274 AC: 2871 AN: 10486

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10579 AN: 67956

Other (OTH) AF: 0.122 AC: 257 AN: 2112

Alfa AF: 0.0999 Hom.: 232

Bravo AF: 0.107

Asia WGS AF: 0.106 AC: 369 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Neuropathy, hereditary sensory and autonomic, type 2A (1)
-	-	1	not provided (1)
-	-	1	Pseudohypoaldosteronism type 2C (1)
-	-	1	Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.57
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.034
SpliceAI score (max)		0.010		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: rs11064573; hg19: chr12-968400; COSMIC: COSV60034163; COSMIC: COSV60034163;