rs2107612

chr12-779154-G-A

Variant summary

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

The NM_213655.5(WNK1):c.759+24830G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,010 control chromosomes in the GnomAD database, including 38,021 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 0.70 (38021 hom., cov: 32)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.759+24830G>A		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.759+24830G>A		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.759+24830G>A		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.759+24830G>A		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107089 AN: 151892 Hom.: 38002 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.705 AC: 107158 AN: 152010 Hom.: 38021 Cov.: 32 AF XY: 0.708 AC XY: 52609 AN XY: 74310

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.682

Alfa AF: 0.720 Hom.: 29135

Bravo AF: 0.701

Asia WGS AF: 0.741 AC: 2572 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.025
Dann	Benign	0.26

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: rs2107612; hg19: chr12-888320; COSMIC: COSV60024787; COSMIC: COSV60024787;