rs4980974

Variant names:

• chr12-875862-G-A
• rs4980974
• NM_213655.5:c.3718-2350G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-875862-G-A
• chr12-875862-G-C
• chr12-875862-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.3718-2350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,030 control chromosomes in the GnomAD database, including 11,928 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 0.39 (11928 hom., cov: 32)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 5 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.3718-2350G>A		intron_variant	Intron 11 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.2224-2350G>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.3718-2350G>A		intron_variant	Intron 11 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.2224-2350G>A		intron_variant	Intron 9 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59051 AN: 151912 Hom.: 11920 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.389 AC: 59083 AN: 152030 Hom.: 11928 Cov.: 32 AF XY: 0.389 AC XY: 28931 AN XY: 74304

African (AFR) AF: 0.277 AC: 11467 AN: 41468

American (AMR) AF: 0.409 AC: 6250 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2702 AN: 5178

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4820

European-Finnish (FIN) AF: 0.433 AC: 4561 AN: 10528

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29859 AN: 67974

Other (OTH) AF: 0.375 AC: 794 AN: 2116

Alfa AF: 0.293 Hom.: 777

Bravo AF: 0.385

Asia WGS AF: 0.400 AC: 1390 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		-0.84
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: rs4980974; hg19: chr12-985028;