rs11739136
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_004137.4(KCNMB1):c.193G>A(p.Glu65Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 1,613,934 control chromosomes in the GnomAD database, including 8,040 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.088 ( 675 hom., cov: 32)
Exomes 𝑓: 0.097 ( 7365 hom. )
Consequence
KCNMB1
NM_004137.4 missense
NM_004137.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 1.17
Genes affected
KCNMB1 (HGNC:6285): (potassium calcium-activated channel subfamily M regulatory beta subunit 1) MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits. [provided by RefSeq, Jul 2008]
KCNIP1 (HGNC:15521): (potassium voltage-gated channel interacting protein 1) This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0013051927).
BP6
?
Variant 5-170383792-C-T is Benign according to our data. Variant chr5-170383792-C-T is described in ClinVar as [Benign]. Clinvar id is 5941.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMB1 | NM_004137.4 | c.193G>A | p.Glu65Lys | missense_variant | 3/4 | ENST00000274629.9 | |
KCNIP1 | NM_001034838.3 | c.88+29828C>T | intron_variant | ||||
KCNIP1 | XM_017009407.2 | c.88+29828C>T | intron_variant | ||||
KCNIP1 | XM_017009408.2 | c.88+29828C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMB1 | ENST00000274629.9 | c.193G>A | p.Glu65Lys | missense_variant | 3/4 | 1 | NM_004137.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0883 AC: 13431AN: 152082Hom.: 676 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
13431
AN:
152082
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: 0.0994 AC: 24974AN: 251146Hom.: 1404 AF XY: 0.0984 AC XY: 13361AN XY: 135748
GnomAD3 exomes
AF:
AC:
24974
AN:
251146
Hom.:
AF XY:
AC XY:
13361
AN XY:
135748
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: 0.0971 AC: 141940AN: 1461734Hom.: 7365 Cov.: 32 AF XY: 0.0965 AC XY: 70195AN XY: 727164
GnomAD4 exome
AF:
AC:
141940
AN:
1461734
Hom.:
Cov.:
32
AF XY:
AC XY:
70195
AN XY:
727164
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: 0.0882 AC: 13431AN: 152200Hom.: 675 Cov.: 32 AF XY: 0.0883 AC XY: 6572AN XY: 74404
GnomAD4 genome
?
AF:
AC:
13431
AN:
152200
Hom.:
Cov.:
32
AF XY:
AC XY:
6572
AN XY:
74404
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
346
ALSPAC
AF:
AC:
408
ESP6500AA
AF:
AC:
266
ESP6500EA
AF:
AC:
870
ExAC
?
AF:
AC:
11588
Asia WGS
AF:
AC:
296
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KCNMB1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 26, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hypertension, diastolic, resistance to Benign:1
protective, no assertion criteria provided | literature only | OMIM | Jan 01, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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