rs11611246

Positions:

• chr12-830314-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_213655.5(WNK1):​c.1311+154G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,986 control chromosomes in the GnomAD database, including 3,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3039 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.386

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-830314-G-T is Benign according to our data. Variant chr12-830314-G-T is described in ClinVar as [Benign]. Clinvar id is 670864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.1311+154G>T		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.1311+154G>T		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.1311+154G>T		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.1311+154G>T		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28954 AN: 151868 Hom.: 3034 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.191 AC: 28963 AN: 151986 Hom.: 3039 Cov.: 31 AF XY: 0.193 AC XY: 14333 AN XY: 74254

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.181

Alfa AF: 0.200 Hom.: 1443

Bravo AF: 0.192

Asia WGS AF: 0.231 AC: 802 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.62

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: rs11611246; hg19: chr12-939480; COSMIC: COSV104410999; COSMIC: COSV104410999;