Variant 3-179250846-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_171830.2(KCNMB3):c.145G>A(p.Ala49Thr) variant causes a missense change. The variant allele was found at a frequency of 0.376 in 1,613,814 control chromosomes in the GnomAD database, including 116,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10431 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106284 hom. )

Consequence

KCNMB3
NM_171830.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

KCNMB3 (HGNC:6287): (potassium calcium-activated channel subfamily M regulatory beta subunit 3) 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 modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22. [provided by RefSeq, Jul 2009]

KCNMB3 links:

KCNMB3 (HGNC:):

KCNMB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023398757).

BP6

Variant 3-179250846-C-T is Benign according to our data. Variant chr3-179250846-C-T is described in ClinVar as [Benign]. Clinvar id is 1250939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB3	NM_171830.2 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	1/3	ENST00000392685.7	NP_741981.1	Q9NPA1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB3	ENST00000392685.7 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	1/3	1	NM_171830.2	ENSP00000376451.2		Q9NPA1-3

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55683

AN:

151922

Hom.:

10426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.600

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.343

AC:

86143

AN:

251440

Hom.:

15503

AF XY:

0.344

AC XY:

46749

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.377

AC:

551239

AN:

1461774

Hom.:

106284

Cov.:

AF XY:

0.375

AC XY:

272789

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.311

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.367

AC:

55728

AN:

152040

Hom.:

10431

Cov.:

AF XY:

0.363

AC XY:

26960

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.382

Hom.:

27850

Bravo

AF:

0.362

TwinsUK

AF:

0.404

AC:

1499

ALSPAC

AF:

0.401

AC:

1546

ESP6500AA

AF:

0.388

AC:

1710

ESP6500EA

AF:

0.382

AC:

3284

ExAC

AF:

0.346

AC:

41962

Asia WGS

AF:

0.211

AC:

734

AN:

3478

EpiCase

AF:

0.391

EpiControl

AF:

0.388

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2020	This variant is associated with the following publications: (PMID: 23826284) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.071

.;.;.;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.83

.;T;T;T;T

MetaRNN

Benign

0.023

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

2.9

.;.;.;M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Uncertain

0.037

.;D;D;D;D

Polyphen

0.99

D;.;D;D;D

Vest4

0.33

MPC

0.36

ClinPred

0.028

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.097

gMVP

0.33

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