12-779262-C-T

Position:

• chr12-779262-C-T

Variant summary

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

The NM_018979.4(WNK1):​c.759+24938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,966 control chromosomes in the GnomAD database, including 40,040 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 0.72 (40040 hom., cov: 31)
• Consequence: WNK1 NM_018979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891

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=-0.95).
• 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	Protein	UniProt
WNK1	NM_213655.5	c.759+24938C>T		intron_variant		ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.759+24938C>T		intron_variant		ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.759+24938C>T		intron_variant		5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.759+24938C>T		intron_variant		1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109514 AN: 151848 Hom.: 40022 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.721 AC: 109576 AN: 151966 Hom.: 40040 Cov.: 31 AF XY: 0.724 AC XY: 53768 AN XY: 74286

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.720

Alfa AF: 0.754 Hom.: 23996

Bravo AF: 0.708

Asia WGS AF: 0.735 AC: 2551 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.3
DANN	Benign	0.43

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: rs2107613; hg19: chr12-888428; COSMIC: COSV60024796; COSMIC: COSV60024796;