12-834787-G-T

Variant names:

• chr12-834787-G-T
• rs11064560
• NM_213655.5:c.1311+4627G>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.1311+4627G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,618 control chromosomes in the GnomAD database, including 31,654 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 0.64 (31654 hom., cov: 29)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 11 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213655.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	NM_213655.5	MANE Plus Clinical	c.1311+4627G>T		intron	N/A	NP_998820.3
	WNK1	NM_018979.4	MANE Select	c.1311+4627G>T		intron	N/A	NP_061852.3
	WNK1	NM_001184985.2		c.1311+4627G>T		intron	N/A	NP_001171914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	ENST00000340908.9	TSL:5 MANE Plus Clinical	c.1311+4627G>T		intron	N/A	ENSP00000341292.5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.1311+4627G>T		intron	N/A	ENSP00000313059.6
	WNK1	ENST00000530271.6	TSL:1	c.1311+4627G>T		intron	N/A	ENSP00000433548.3

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96557 AN: 151500 Hom.: 31641 Cov.: 29

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.637 AC: 96615 AN: 151618 Hom.: 31654 Cov.: 29 AF XY: 0.641 AC XY: 47493 AN XY: 74094

African (AFR) AF: 0.481 AC: 19829 AN: 41238

American (AMR) AF: 0.685 AC: 10418 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2041 AN: 3464

East Asian (EAS) AF: 0.874 AC: 4520 AN: 5174

South Asian (SAS) AF: 0.684 AC: 3278 AN: 4792

European-Finnish (FIN) AF: 0.742 AC: 7811 AN: 10528

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46572 AN: 67900

Other (OTH) AF: 0.613 AC: 1292 AN: 2106

Alfa AF: 0.661 Hom.: 88983

Bravo AF: 0.626

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.18
PhyloP100		-1.5
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: rs11064560; hg19: chr12-943953;