rs149861510
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000890.5(KCNJ5):c.837G>A(p.Glu279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00078 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000091 ( 0 hom. )
Consequence
KCNJ5
NM_000890.5 synonymous
NM_000890.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]
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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=-0.47).
BP6
?
Variant 11-128912110-G-A is Benign according to our data. Variant chr11-128912110-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 412767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.71 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000091 (133/1461302) while in subpopulation AFR AF= 0.00335 (112/33480). AF 95% confidence interval is 0.00284. There are 0 homozygotes in gnomad4_exome. There are 54 alleles in male gnomad4_exome subpopulation. Median coverage is 47. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 119 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ5 | NM_000890.5 | c.837G>A | p.Glu279= | synonymous_variant | 2/3 | ENST00000529694.6 | |
KCNJ5 | NM_001354169.2 | c.837G>A | p.Glu279= | synonymous_variant | 3/4 | ||
KCNJ5 | XM_011542810.4 | c.837G>A | p.Glu279= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ5 | ENST00000529694.6 | c.837G>A | p.Glu279= | synonymous_variant | 2/3 | 1 | NM_000890.5 | P1 | |
KCNJ5 | ENST00000338350.4 | c.837G>A | p.Glu279= | synonymous_variant | 3/4 | 1 | P1 | ||
KCNJ5 | ENST00000533599.1 | c.837G>A | p.Glu279= | synonymous_variant | 1/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000775 AC: 118AN: 152214Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000202 AC: 50AN: 248054Hom.: 1 AF XY: 0.000127 AC XY: 17AN XY: 134214
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GnomAD4 exome AF: 0.0000910 AC: 133AN: 1461302Hom.: 0 Cov.: 47 AF XY: 0.0000743 AC XY: 54AN XY: 726920
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GnomAD4 genome ? AF: 0.000781 AC: 119AN: 152332Hom.: 0 Cov.: 34 AF XY: 0.000644 AC XY: 48AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KCNJ5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 14, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2021 | This variant is associated with the following publications: (PMID: 29726953) - |
Long QT syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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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