chr11-128911918-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000890.5(KCNJ5):c.645G>A(p.Leu215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000468 in 1,603,918 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 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
KCNJ5
NM_000890.5 synonymous
NM_000890.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.40
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 11-128911918-G-A is Benign according to our data. Variant chr11-128911918-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 527073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.4 with no splicing effect.
BS2
High AC in GnomAd4 at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ5 | NM_000890.5 | c.645G>A | p.Leu215= | synonymous_variant | 2/3 | ENST00000529694.6 | |
KCNJ5 | NM_001354169.2 | c.645G>A | p.Leu215= | synonymous_variant | 3/4 | ||
KCNJ5 | XM_011542810.4 | c.645G>A | p.Leu215= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ5 | ENST00000529694.6 | c.645G>A | p.Leu215= | synonymous_variant | 2/3 | 1 | NM_000890.5 | P1 | |
KCNJ5 | ENST00000338350.4 | c.645G>A | p.Leu215= | synonymous_variant | 3/4 | 1 | P1 | ||
KCNJ5 | ENST00000533599.1 | c.645G>A | p.Leu215= | synonymous_variant | 1/2 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000486 AC: 12AN: 247114Hom.: 0 AF XY: 0.0000300 AC XY: 4AN XY: 133298
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GnomAD4 exome AF: 0.0000310 AC: 45AN: 1451708Hom.: 0 Cov.: 59 AF XY: 0.0000278 AC XY: 20AN XY: 720320
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GnomAD4 genome AF: 0.000197 AC: 30AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74346
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ClinVar
Significance: 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 | Jun 20, 2019 | 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). - |
Long QT syndrome 13;C3838758:Familial hyperaldosteronism type III Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 14, 2022 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 13, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at