chr5-170383792-C-T

Position:

chr5-170383792-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000274629.9(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,protective (no stars).

Frequency

Genomes: 𝑓 0.088 ( 675 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7365 hom. )

Consequence

KCNMB1
ENST00000274629.9 missense

Scores

Clinical Significance

Benign; protective no assertion criteria provided B:2

Conservation

PhyloP100: 1.17

Variant links:

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]

KCNMB1 links:

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]

KCNIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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, protective]. Clinvar id is 5941.Status of the report is no_assertion_criteria_provided, 0 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	Protein
KCNMB1	NM_004137.4 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	3/4	ENST00000274629.9	NP_004128.1
KCNIP1	NM_001034838.3 linkuse as main transcript	c.88+29828C>T		intron_variant			NP_001030010.1
KCNIP1	XM_017009407.2 linkuse as main transcript	c.88+29828C>T		intron_variant			XP_016864896.1
KCNIP1	XM_017009408.2 linkuse as main transcript	c.88+29828C>T		intron_variant			XP_016864897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB1	ENST00000274629.9 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	3/4	1	NM_004137.4	ENSP00000274629	P1	Q16558-1

Frequencies

GnomAD3 genomes

AF:

0.0883

AC:

13431

AN:

152082

Hom.:

676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0560

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0723

Gnomad FIN

AF:

0.0686

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0952

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0994

AC:

24974

AN:

251146

Hom.:

1404

AF XY:

0.0984

AC XY:

13361

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.0566

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.0955

Gnomad SAS exome

AF:

0.0741

Gnomad FIN exome

AF:

0.0691

Gnomad NFE exome

AF:

0.0961

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.0971

AC:

141940

AN:

1461734

Hom.:

7365

Cov.:

AF XY:

0.0965

AC XY:

70195

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0540

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.0772

Gnomad4 FIN exome

AF:

0.0687

Gnomad4 NFE exome

AF:

0.0969

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0882

AC:

13431

AN:

152200

Hom.:

675

Cov.:

AF XY:

0.0883

AC XY:

6572

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0558

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0725

Gnomad4 FIN

AF:

0.0686

Gnomad4 NFE

AF:

0.0952

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0989

Hom.:

2016

Bravo

AF:

0.0940

TwinsUK

AF:

0.0933

AC:

346

ALSPAC

AF:

0.106

AC:

408

ESP6500AA

AF:

0.0604

AC:

266

ESP6500EA

AF:

0.101

AC:

870

ExAC

AF:

0.0954

AC:

11588

Asia WGS

AF:

0.0850

AC:

296

AN:

3478

EpiCase

AF:

0.0948

EpiControl

AF:

0.0957

ClinVar

Significance: Benign; protective

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCNMB1-related disorder

Benign:1

Benign, no assertion criteria provided

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.68

N;N

MutationTaster

Benign

1.1e-14

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.053

Sift

Benign

0.17

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.051

B;B

Vest4

0.22

MPC

0.13

ClinPred

0.0040

GERP RS

3.6

Varity_R

0.12

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over