rs17221805
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002234.4(KCNA5):c.1497G>A(p.Leu499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000762 in 1,614,218 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 6 hom. )
Consequence
KCNA5
NM_002234.4 synonymous
NM_002234.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.07
Genes affected
KCNA5 (HGNC:6224): (potassium voltage-gated channel subfamily A member 5) Potassium channels represent the most complex class of voltage-gated ino channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, the function of which could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion. This gene is intronless, and the gene is clustered with genes KCNA1 and KCNA6 on chromosome 12. Defects in this gene are a cause of familial atrial fibrillation type 7 (ATFB7). [provided by RefSeq, May 2012]
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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=-0.5).
BP6
?
Variant 12-5045644-G-A is Benign according to our data. Variant chr12-5045644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 469584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-5045644-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.07 with no splicing effect.
BS2
?
High AC in GnomAd4 at 631 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNA5 | NM_002234.4 | c.1497G>A | p.Leu499= | synonymous_variant | 1/1 | ENST00000252321.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNA5 | ENST00000252321.5 | c.1497G>A | p.Leu499= | synonymous_variant | 1/1 | NM_002234.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00414 AC: 630AN: 152212Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00111 AC: 279AN: 251454Hom.: 4 AF XY: 0.000773 AC XY: 105AN XY: 135900
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GnomAD4 exome AF: 0.000410 AC: 599AN: 1461888Hom.: 6 Cov.: 34 AF XY: 0.000344 AC XY: 250AN XY: 727244
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GnomAD4 genome ? AF: 0.00414 AC: 631AN: 152330Hom.: 5 Cov.: 32 AF XY: 0.00419 AC XY: 312AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Atrial fibrillation, familial, 7 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 07, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2021 | - - |
Computational scores
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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