12-793913-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213655.5(WNK1):c.760-19729T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,978 control chromosomes in the GnomAD database, including 32,092 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 0.64 (32092 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.760-19729T>C		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.760-19729T>C		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.760-19729T>C		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.760-19729T>C		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97369 AN: 151860 Hom.: 32080 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.641 AC: 97426 AN: 151978 Hom.: 32092 Cov.: 31 AF XY: 0.645 AC XY: 47880 AN XY: 74284

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.618

Alfa AF: 0.646 Hom.: 4320

Bravo AF: 0.631

Asia WGS AF: 0.716 AC: 2485 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.83
Dann	Benign	0.47

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: rs2107614; hg19: chr12-903079;