chr12-860634-G-T

Variant names:

• chr12-860634-G-T
• rs12816718
• NM_213655.5:c.1621-379G>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.1621-379G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,166 control chromosomes in the GnomAD database, including 2,234 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 0.17 (2234 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.1621-379G>T		intron_variant	Intron 6 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.1621-379G>T		intron_variant	Intron 6 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.1621-379G>T		intron_variant	Intron 6 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.1621-379G>T		intron_variant	Intron 6 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25131 AN: 152048 Hom.: 2230 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.165 AC: 25161 AN: 152166 Hom.: 2234 Cov.: 31 AF XY: 0.168 AC XY: 12493 AN XY: 74368

African (AFR) AF: 0.185 AC: 7698 AN: 41502

American (AMR) AF: 0.104 AC: 1596 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.0611 AC: 317 AN: 5186

South Asian (SAS) AF: 0.178 AC: 856 AN: 4812

European-Finnish (FIN) AF: 0.272 AC: 2881 AN: 10576

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10692 AN: 68006

Other (OTH) AF: 0.149 AC: 315 AN: 2112

Alfa AF: 0.162 Hom.: 1209

Bravo AF: 0.153

Asia WGS AF: 0.121 AC: 421 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	1.6
DANN	Benign	0.52
PhyloP100		0.043
PromoterAI		-0.031	Neutral
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: rs12816718; hg19: chr12-969800;