20-49373007-T-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004975.4(KCNB1):c.2553A>G(p.Gly851Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,774 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
KCNB1
NM_004975.4 synonymous
NM_004975.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.472
Publications
0 publications found
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]
KCNB1 Gene-Disease associations (from GenCC):
- complex neurodevelopmental disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- developmental and epileptic encephalopathy, 26Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 20-49373007-T-C is Benign according to our data. Variant chr20-49373007-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2196208.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.472 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| KCNB1 | NM_004975.4 | c.2553A>G | p.Gly851Gly | synonymous_variant | Exon 2 of 2 | ENST00000371741.6 | NP_004966.1 | |
| KCNB1 | XM_011528799.3 | c.2553A>G | p.Gly851Gly | synonymous_variant | Exon 3 of 3 | XP_011527101.1 | ||
| LOC105372649 | XR_001754659.2 | n.1201+40983T>C | intron_variant | Intron 2 of 3 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152040Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152040
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460734Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726682 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1460734
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
726682
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33438
American (AMR)
AF:
AC:
0
AN:
44654
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26046
East Asian (EAS)
AF:
AC:
0
AN:
39688
South Asian (SAS)
AF:
AC:
0
AN:
86114
European-Finnish (FIN)
AF:
AC:
0
AN:
53378
Middle Eastern (MID)
AF:
AC:
0
AN:
5568
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111530
Other (OTH)
AF:
AC:
1
AN:
60318
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152040
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74260
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41374
American (AMR)
AF:
AC:
0
AN:
15252
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68006
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 26 Benign:1
Aug 05, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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