rs1159744

Variant names:

• chr12-825679-C-G
• rs1159744
• NM_213655.5:c.933-1363C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-825679-C-G
• chr12-825679-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.933-1363C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,032 control chromosomes in the GnomAD database, including 43,957 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 0.76 (43957 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• 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: 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.933-1363C>G		intron_variant	Intron 2 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.933-1363C>G		intron_variant	Intron 2 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.933-1363C>G		intron_variant	Intron 2 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.933-1363C>G		intron_variant	Intron 2 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115407 AN: 151912 Hom.: 43911 Cov.: 31

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.760 AC: 115508 AN: 152032 Hom.: 43957 Cov.: 31 AF XY: 0.763 AC XY: 56659 AN XY: 74306

African (AFR) AF: 0.744 AC: 30855 AN: 41460

American (AMR) AF: 0.769 AC: 11752 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3468

East Asian (EAS) AF: 0.875 AC: 4534 AN: 5184

South Asian (SAS) AF: 0.761 AC: 3668 AN: 4822

European-Finnish (FIN) AF: 0.813 AC: 8562 AN: 10528

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51216 AN: 67964

Other (OTH) AF: 0.735 AC: 1554 AN: 2114

Alfa AF: 0.759 Hom.: 5453

Bravo AF: 0.756

Asia WGS AF: 0.776 AC: 2681 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		-0.059
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: rs1159744; hg19: chr12-934845;