chr12-800565-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_213655.5(WNK1):​c.760-13077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,850 control chromosomes in the GnomAD database, including 1,414 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 0.12 ( 1414 hom., cov: 32)

Consequence

WNK1
NM_213655.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.235

Publications

5 publications found
Variant links:
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]
WNK1 Gene-Disease associations (from GenCC):
  • neuropathy, hereditary sensory and autonomic, type 2A
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
  • pseudohypoaldosteronism type 2C
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • hereditary sensory and autonomic neuropathy type 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNK1NM_213655.5 linkc.760-13077A>G intron_variant Intron 1 of 27 ENST00000340908.9 NP_998820.3 Q9H4A3-5
WNK1NM_018979.4 linkc.760-13077A>G intron_variant Intron 1 of 27 ENST00000315939.11 NP_061852.3 Q9H4A3-1A5D8Z4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WNK1ENST00000340908.9 linkc.760-13077A>G intron_variant Intron 1 of 27 5 NM_213655.5 ENSP00000341292.5 Q9H4A3-5
WNK1ENST00000315939.11 linkc.760-13077A>G intron_variant Intron 1 of 27 1 NM_018979.4 ENSP00000313059.6 Q9H4A3-1

Frequencies

GnomAD3 genomes
AF:
0.121
AC:
18393
AN:
151732
Hom.:
1409
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.200
Gnomad AMI
AF:
0.163
Gnomad AMR
AF:
0.174
Gnomad ASJ
AF:
0.119
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.0256
Gnomad FIN
AF:
0.0840
Gnomad MID
AF:
0.0446
Gnomad NFE
AF:
0.0829
Gnomad OTH
AF:
0.123
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.121
AC:
18432
AN:
151850
Hom.:
1414
Cov.:
32
AF XY:
0.120
AC XY:
8898
AN XY:
74190
show subpopulations
African (AFR)
AF:
0.200
AC:
8292
AN:
41402
American (AMR)
AF:
0.174
AC:
2662
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.119
AC:
413
AN:
3468
East Asian (EAS)
AF:
0.000578
AC:
3
AN:
5188
South Asian (SAS)
AF:
0.0261
AC:
125
AN:
4798
European-Finnish (FIN)
AF:
0.0840
AC:
883
AN:
10514
Middle Eastern (MID)
AF:
0.0548
AC:
16
AN:
292
European-Non Finnish (NFE)
AF:
0.0829
AC:
5632
AN:
67914
Other (OTH)
AF:
0.122
AC:
258
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
777
1554
2332
3109
3886
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
194
388
582
776
970
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.101
Hom.:
1123
Bravo
AF:
0.134
Asia WGS
AF:
0.0330
AC:
113
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
2.6
DANN
Benign
0.63
PhyloP100
-0.23
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12314329; hg19: chr12-909731; API