rs141971833
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_213655.5(WNK1):āc.4410A>Gā(p.Ser1470=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,614,212 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0039 ( 4 hom., cov: 33)
Exomes š: 0.0024 ( 82 hom. )
Consequence
WNK1
NM_213655.5 synonymous
NM_213655.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.88
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 12-883559-A-G is Benign according to our data. Variant chr12-883559-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 310820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-883559-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.88 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00395 (601/152342) while in subpopulation SAS AF= 0.0319 (154/4822). AF 95% confidence interval is 0.0278. There are 4 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.4410A>G | p.Ser1470= | synonymous_variant | 16/28 | ENST00000340908.9 | |
WNK1 | NM_018979.4 | c.3654A>G | p.Ser1218= | synonymous_variant | 16/28 | ENST00000315939.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.4410A>G | p.Ser1470= | synonymous_variant | 16/28 | 5 | NM_213655.5 | A2 | |
WNK1 | ENST00000315939.11 | c.3654A>G | p.Ser1218= | synonymous_variant | 16/28 | 1 | NM_018979.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00395 AC: 602AN: 152224Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00465 AC: 1170AN: 251406Hom.: 26 AF XY: 0.00560 AC XY: 761AN XY: 135898
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GnomAD4 exome AF: 0.00237 AC: 3461AN: 1461870Hom.: 82 Cov.: 33 AF XY: 0.00309 AC XY: 2246AN XY: 727236
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GnomAD4 genome ? AF: 0.00395 AC: 601AN: 152342Hom.: 4 Cov.: 33 AF XY: 0.00428 AC XY: 319AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 03, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 05, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
Pseudohypoaldosteronism type 2C Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at