rs520282
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004975.4(KCNB1):c.198C>T(p.His66=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,612,228 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 164 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 125 hom. )
Consequence
KCNB1
NM_004975.4 synonymous
NM_004975.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.346
Genes affected
KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion 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, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]
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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=-0.57).
BP6
?
Variant 20-49482283-G-A is Benign according to our data. Variant chr20-49482283-G-A is described in ClinVar as [Benign]. Clinvar id is 380821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.346 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNB1 | NM_004975.4 | c.198C>T | p.His66= | synonymous_variant | 1/2 | ENST00000371741.6 | |
KCNB1 | XM_011528799.3 | c.198C>T | p.His66= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNB1 | ENST00000371741.6 | c.198C>T | p.His66= | synonymous_variant | 1/2 | 1 | NM_004975.4 | P1 | |
KCNB1 | ENST00000635465.1 | c.198C>T | p.His66= | synonymous_variant | 2/3 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0248 AC: 3774AN: 152232Hom.: 164 Cov.: 32
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GnomAD3 exomes AF: 0.00675 AC: 1668AN: 246960Hom.: 57 AF XY: 0.00517 AC XY: 694AN XY: 134320
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GnomAD4 exome AF: 0.00280 AC: 4085AN: 1459878Hom.: 125 Cov.: 31 AF XY: 0.00246 AC XY: 1787AN XY: 726030
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GnomAD4 genome ? AF: 0.0248 AC: 3776AN: 152350Hom.: 164 Cov.: 32 AF XY: 0.0237 AC XY: 1767AN XY: 74504
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2016 | 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. - |
Developmental and epileptic encephalopathy, 26 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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at