rs751308084
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The ENST00000371741.6(KCNB1):āc.2049A>Cā(p.Pro683=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,702 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000013 ( 0 hom. )
Consequence
KCNB1
ENST00000371741.6 synonymous
ENST00000371741.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.918
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 20-49373511-T-G is Benign according to our data. Variant chr20-49373511-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 475259.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.918 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000013 (19/1461850) while in subpopulation EAS AF= 0.000453 (18/39698). AF 95% confidence interval is 0.000293. There are 0 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNB1 | NM_004975.4 | c.2049A>C | p.Pro683= | synonymous_variant | 2/2 | ENST00000371741.6 | NP_004966.1 | |
LOC105372649 | XR_001754659.2 | n.1201+41487T>G | intron_variant, non_coding_transcript_variant | |||||
KCNB1 | XM_011528799.3 | c.2049A>C | p.Pro683= | synonymous_variant | 3/3 | XP_011527101.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNB1 | ENST00000371741.6 | c.2049A>C | p.Pro683= | synonymous_variant | 2/2 | 1 | NM_004975.4 | ENSP00000360806 | P1 | |
KCNB1 | ENST00000635465.1 | c.2049A>C | p.Pro683= | synonymous_variant | 3/3 | 1 | ENSP00000489193 | P1 | ||
ENST00000637341.1 | n.206+41487T>G | intron_variant, non_coding_transcript_variant | 5 | |||||||
KCNB1 | ENST00000635878.1 | c.97-74128A>C | intron_variant | 5 | ENSP00000489908 |
Frequencies
GnomAD3 genomes AF: 0.00000663 AC: 1AN: 150852Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
150852
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:
GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251188Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135752
GnomAD3 exomes
AF:
AC:
23
AN:
251188
Hom.:
AF XY:
AC XY:
9
AN XY:
135752
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461850Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727234
GnomAD4 exome
AF:
AC:
19
AN:
1461850
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
727234
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000663 AC: 1AN: 150852Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73616
GnomAD4 genome
AF:
AC:
1
AN:
150852
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
73616
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
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
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 14, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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