rs4980973

Variant names:

• chr12-873880-G-A
• rs4980973
• NM_213655.5:c.3717+2532G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-873880-G-A
• chr12-873880-G-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.3717+2532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,886 control chromosomes in the GnomAD database, including 1,722 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 0.14 (1722 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.3717+2532G>A		intron_variant	Intron 11 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.2223+2532G>A		intron_variant	Intron 9 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.3717+2532G>A		intron_variant	Intron 11 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.2223+2532G>A		intron_variant	Intron 9 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21131 AN: 151768 Hom.: 1721 Cov.: 31

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.139 AC: 21133 AN: 151886 Hom.: 1722 Cov.: 31 AF XY: 0.139 AC XY: 10300 AN XY: 74244

African (AFR) AF: 0.0869 AC: 3599 AN: 41398

American (AMR) AF: 0.115 AC: 1750 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2105 AN: 5154

South Asian (SAS) AF: 0.119 AC: 574 AN: 4820

European-Finnish (FIN) AF: 0.152 AC: 1599 AN: 10532

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10565 AN: 67964

Other (OTH) AF: 0.130 AC: 272 AN: 2098

Alfa AF: 0.127 Hom.: 5770

Bravo AF: 0.136

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		0.012
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: rs4980973; hg19: chr12-983046;