NM_213655.5:c.1312-1821G>A

Variant names:

• chr12-855340-G-A
• rs6489756
• NM_213655.5:c.1312-1821G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213655.5(WNK1):​c.1312-1821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,070 control chromosomes in the GnomAD database, including 20,112 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 0.51 (20112 hom., cov: 32)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.1312-1821G>A		intron_variant	Intron 4 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.1312-1821G>A		intron_variant	Intron 4 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.1312-1821G>A		intron_variant	Intron 4 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.1312-1821G>A		intron_variant	Intron 4 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77184 AN: 151952 Hom.: 20107 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.508 AC: 77231 AN: 152070 Hom.: 20112 Cov.: 32 AF XY: 0.508 AC XY: 37767 AN XY: 74352

African (AFR) AF: 0.433 AC: 17937 AN: 41456

American (AMR) AF: 0.586 AC: 8955 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1493 AN: 3468

East Asian (EAS) AF: 0.812 AC: 4205 AN: 5178

South Asian (SAS) AF: 0.515 AC: 2483 AN: 4820

European-Finnish (FIN) AF: 0.470 AC: 4964 AN: 10562

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35560 AN: 67980

Other (OTH) AF: 0.486 AC: 1025 AN: 2108

Alfa AF: 0.442 Hom.: 2123

Bravo AF: 0.515

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.21
Mutation Taster		=99/1	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: rs6489756; hg19: chr12-964506;