11-128916399-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000890.5(KCNJ5):c.938-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,608,824 control chromosomes in the GnomAD database, including 423,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.74 ( 42221 hom., cov: 32)
Exomes 𝑓: 0.72 ( 381386 hom. )
Consequence
KCNJ5
NM_000890.5 splice_polypyrimidine_tract, intron
NM_000890.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00004011
2
Clinical Significance
Conservation
PhyloP100: -0.677
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 11-128916399-G-A is Benign according to our data. Variant chr11-128916399-G-A is described in ClinVar as [Benign]. Clinvar id is 137995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128916399-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ5 | NM_000890.5 | c.938-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000529694.6 | |||
KCNJ5 | NM_001354169.2 | c.938-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
KCNJ5 | XM_011542810.4 | c.938-10G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ5 | ENST00000529694.6 | c.938-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000890.5 | P1 | |||
KCNJ5 | ENST00000338350.4 | c.938-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
KCNJ5 | ENST00000533599.1 | c.938-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.743 AC: 112980AN: 152026Hom.: 42202 Cov.: 32
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GnomAD3 exomes AF: 0.731 AC: 183011AN: 250316Hom.: 67038 AF XY: 0.734 AC XY: 99343AN XY: 135400
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GnomAD4 exome AF: 0.723 AC: 1052544AN: 1456680Hom.: 381386 Cov.: 34 AF XY: 0.726 AC XY: 526065AN XY: 725010
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GnomAD4 genome AF: 0.743 AC: 113049AN: 152144Hom.: 42221 Cov.: 32 AF XY: 0.742 AC XY: 55187AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 04, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Familial hyperaldosteronism type III Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
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. - |
Long QT syndrome 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Congenital long QT syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Long QT syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at