rs749215518
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_004975.4(KCNB1):c.1207C>T(p.Leu403Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,172 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
KCNB1
NM_004975.4 synonymous
NM_004975.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.54
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 20-49374353-G-A is Benign according to our data. Variant chr20-49374353-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475256.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.54 with no splicing effect.
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNB1 | NM_004975.4 | c.1207C>T | p.Leu403Leu | synonymous_variant | 2/2 | ENST00000371741.6 | NP_004966.1 | |
KCNB1 | XM_011528799.3 | c.1207C>T | p.Leu403Leu | synonymous_variant | 3/3 | XP_011527101.1 | ||
LOC105372649 | XR_001754659.2 | n.1201+42329G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNB1 | ENST00000371741.6 | c.1207C>T | p.Leu403Leu | synonymous_variant | 2/2 | 1 | NM_004975.4 | ENSP00000360806.3 | ||
KCNB1 | ENST00000635465.1 | c.1207C>T | p.Leu403Leu | synonymous_variant | 3/3 | 1 | ENSP00000489193.1 | |||
KCNB1 | ENST00000635878.1 | c.97-74970C>T | intron_variant | 5 | ENSP00000489908.1 | |||||
ENSG00000290421 | ENST00000637341.1 | n.206+42329G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250506Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135482
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GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460962Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 726848
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
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ClinVar
Significance: Benign/Likely 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 | Athena Diagnostics | Sep 30, 2024 | - - |
Developmental and epileptic encephalopathy, 26 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2023 | - - |
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