rs11739136

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 14/21 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
NM_004137.4 missense

Scores

Clinical Significance

Benign; protective no assertion criteria provided B:2

Conservation

PhyloP100: 1.17

Publications

73 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
KCNMB1	NM_004137.4 link	c.193G>A	p.Glu65Lys	missense_variant	Exon 3 of 4	ENST00000274629.9	NP_004128.1	Q16558-1
KCNIP1	NM_001034838.3 link	c.88+29828C>T		intron_variant	Intron 1 of 7		NP_001030010.1	Q9NZI2-4
KCNIP1	XM_017009407.2 link	c.88+29828C>T		intron_variant	Intron 2 of 8		XP_016864896.1	Q9NZI2-4
KCNIP1	XM_017009408.2 link	c.88+29828C>T		intron_variant	Intron 1 of 3		XP_016864897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB1	ENST00000274629.9 link	c.193G>A	p.Glu65Lys	missense_variant	Exon 3 of 4	1	NM_004137.4	ENSP00000274629.3		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

GnomAD2 exomes

AF:

0.0994

AC:

24974

AN:

251146

AF XY:

0.0984

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 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

African (AFR)

AF:

0.0540

AC:

1808

AN:

33480

American (AMR)

AF:

0.147

AC:

6559

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4655

AN:

26134

East Asian (EAS)

AF:

0.103

AC:

4071

AN:

39700

South Asian (SAS)

AF:

0.0772

AC:

6659

AN:

86252

European-Finnish (FIN)

AF:

0.0687

AC:

3669

AN:

53410

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5766

European-Non Finnish (NFE)

AF:

0.0969

AC:

107772

AN:

1111910

Other (OTH)

AF:

0.101

AC:

6124

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7533

15066

22598

30131

37664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4018

8036

12054

16072

20090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0882

AC:

13431

AN:

152200

Hom.:

675

Cov.:

AF XY:

0.0883

AC XY:

6572

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0558

AC:

2319

AN:

41526

American (AMR)

AF:

0.133

AC:

2031

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3472

East Asian (EAS)

AF:

0.114

AC:

591

AN:

5176

South Asian (SAS)

AF:

0.0725

AC:

350

AN:

4826

European-Finnish (FIN)

AF:

0.0686

AC:

726

AN:

10584

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0952

AC:

6473

AN:

68010

Other (OTH)

AF:

0.100

AC:

212

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

612

1224

1837

2449

3061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0974

Hom.:

3748

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

Nov 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Jan 01, 2005

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

1.2

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over