chr20-49373029-A-G
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2
The NM_004975.4(KCNB1):āc.2531T>Cā(p.Leu844Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,742 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 Benign (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000020 ( 0 hom. )
Consequence
KCNB1
NM_004975.4 missense
NM_004975.4 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 3.33
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 -7 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KCNB1. . Gene score misZ 4.269 (greater than the threshold 3.09). Trascript score misZ 5.3923 (greater than threshold 3.09). GenCC has associacion of gene with undetermined early-onset epileptic encephalopathy, complex neurodevelopmental disorder, developmental and epileptic encephalopathy, 26.
BP4
Computational evidence support a benign effect (MetaRNN=0.21908373).
BP6
Variant 20-49373029-A-G is Benign according to our data. Variant chr20-49373029-A-G is described in ClinVar as [Benign]. Clinvar id is 1502238.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNB1 | NM_004975.4 | c.2531T>C | p.Leu844Ser | missense_variant | 2/2 | ENST00000371741.6 | NP_004966.1 | |
LOC105372649 | XR_001754659.2 | n.1201+41005A>G | intron_variant, non_coding_transcript_variant | |||||
KCNB1 | XM_011528799.3 | c.2531T>C | p.Leu844Ser | missense_variant | 3/3 | XP_011527101.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNB1 | ENST00000371741.6 | c.2531T>C | p.Leu844Ser | missense_variant | 2/2 | 1 | NM_004975.4 | ENSP00000360806 | P1 | |
ENST00000637341.1 | n.206+41005A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251088Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135698
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461742Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727168
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 26 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of glycosylation at L844 (P = 0.0054);Gain of glycosylation at L844 (P = 0.0054);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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