12-906303-G-C

Position:

• chr12-906303-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_213655.5(WNK1):​c.7400-1544G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 984,976 control chromosomes in the GnomAD database, including 18,242 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 (2039 hom., cov: 31)
  • Exomes 𝑓: 0.19 (16203 hom.)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.6644-1544G>C		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.7400-1544G>C		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.6644-1544G>C		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.7400-1544G>C		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22011 AN: 151916 Hom.: 2037 Cov.: 31

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.193 AC: 161012 AN: 832942 Hom.: 16203 Cov.: 28 AF XY: 0.192 AC XY: 73952 AN XY: 384646

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0752

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.145 AC: 22014 AN: 152034 Hom.: 2039 Cov.: 31 AF XY: 0.146 AC XY: 10860 AN XY: 74290

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0872

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.130

Alfa AF: 0.108 Hom.: 202

Bravo AF: 0.141

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2286028; hg19: chr12-1015469;